bluuebunny/crossref_metadata_2025 huggingface dataset:
A Note on the Occurrence of Catallagia dacenkoi Ioff in North America, with the Description of a Nearctic Subspecies (Siphonaptera: Neopsyllidae)
Authors: Holland George P.
Published: January 2010

As the flea fauna of mammals of northern North America becomes better known, its very close affinity with that of temperate and northern Asia becomes more apparent. Many of the genera are holarctic and are associated with holarctic genera of mammals. In a few instances, the fleas of the Old World and the New World are so similar in morphological details and host association that they are regarded as subspecies. For example, Amphipsylla sibirica (Wagner), Malaraeus penicilliger (Grube), Megabothris calcarifer (Wagner), and Hoplopsyllus
glacialis (Taschenberg) have representatives in both the nearctic and the palaearctic regions. To this list must now be added Catallagia dacenkoi Ioff, a parasite of Microtinae; this species was described originally (Ioff, 1940, pp. 216-217) from the Altai Mountains of central Russia, and a new subspecies has now been discovered in northern Canada and Alaska.
Some Synonymy and New Combinations in Chalcidoidea (Hymenoptera)
Authors: Gahan A. B.
Published: January 2010

At the time of my retirement on December 31, 1950, a number of notes on synonymy and generic transfers had accumulated. Many of these are thought worthy of publication and this paper is made up of a number of them. Those included notes which deal with Nearctic forms will clarify the treatment of certlin genera and species in the catalog of North American Hymenoptera, now in process of publication by the U.S. Department of Agiculture, the Chalcidoidea section of which catalog has assembled and edited by O. Peck of the Canadian Department of Agriculture but which is based in great part upon the classification and arrangement of the collection in the United States National Museum. The catalog will probably appear in print before this paper does. Several notes dealing with forms not known to occur in the Nearctic region, hence not appearing in the catalog, are also included.
A Survey for Grasshopper Parasites in Temperate South America
Authors: Lloyd D. C.
Published: January 2010

In 1937-38 the Argentine Department of Agriculture initiated an exchange of grasshopper parasite material with the Canadian Department of Agriculture which was engaged in a study of the natural control of grasshoppers in various provinces of Canada. By 1942 it was considered desirable to introduce exotic species of parasites into Canada on as wide a scale as possible, and the temperate regions of South America were selected as being the most promising for a survey. The parts of the temperate zone of South America to which preferential attention was to be given included the countries of Uruguay, Argentina, and Chile. The well known grasslands of the Rio de la Plata area have been partially transformed into one of the world centres for cereal production and as in other parts of the world increased grasshopper populations constitute a major problem in the agriculture of the region. Here species of the genus Dichroplus are frequently pests in the way in which members of the closely related Melanoplus are in North America.
Mass Flights of the Spruce Budworm
Authors: Henson W. R.
Published: January 2010

During the course of an investigation of the dispersal of the spruce budwonm (Henson, 1950), mass flights of the insect have been studied. The records of these flights are to be found in the files of the Forest Insect Laboratory, Sault Ste. Marie, Ontario, but in many cases these records are not complete. Nineteen flights for which sufficient data exist have been examined.
An Annotated List of Lepidopterous Larvae from Commercial Blueberry Fields, Charlotte County, N.B.
Authors: Wood G. W.
Published: January 2010

A comprehensive study of insects affecting the low-bush blueberry in New Rrunswick was begun in 1946 largely because of the destructive outbreak of Actebia fennica (Tausch.) in 1944 and 1945. The work was carried on in Charlotte County, where most of the commercial blueberry areas of the Province are located. This paper deals only with the lepidopterous larvae, among which are found the most important pests, such as climbing cutworms, loopers, and leaf tiers.
The Geographic Variation of Dasyuris polata (Duponchel) in North America (Lepidoptera: Geometridae)
Authors: Munroe Eugene
Published: January 2010

The arctic species Dasyuris polata, described by Duponchel (1830: 402; Pl. 199, Fig. 4) from northern Europe, has been known from America since early times. The species is notoriously variable; until recently, however, it has not been possible to assess the geographic components of its variation.

There are now, largely as a product of the Northern Insect Survey, excellent series of D. polata in the Canadian National Collection. Through the kindness of correspondents I have been able to supplement these series by borrowing material of certain non-Canadian forms, and it has become evident that D. polata has striking geographic variation in North America.
Notes on Phanerotoma tibialis (Hald.) and P. fasciata Prov., with Descriptions of Two New Species (Hymenoptera: Braconidae)
Authors: Walley G. Stuart
Published: January 2010

For many years American workers have applied the name Phanerotoma tibialis (Hald.) indiscriminately to specimens reared from a variety of lepidoprerous hosts pertaining to the genera Acrobasis, Carpocapsa, Grapholitha, Laspeyresia, Melissopus, and Tetralopha. Concurrently tibialis has come to be regarded as an unusually variable species in both structure and colour. Recently, after examining many specimens reared from the above hosts, I reached the conclusion that two species of Phanerotoma are involved, one a parasite of Pyralidae of the phycitid and epipachiinid groups, and the other a species that apparently confines its attacks to certain Olethreutidae of the subfamily Eucosminae. For reasons stated below it appears that the name Phanerotoma tibialis (Hald.) applies correctly to the species with pyralid hosts (Acrobasis, Tetrarlopha), whereas the species reared from Olethreutidae (Carpocapsa, Grapholitha, Laspeyresia, Melissopus) should he called Phanerotoma fasciata Prov.
A Review of the North American Species of Herina Robineau-Desvoidy (=Tephronota Loew) (Diptera: Otitidae)
Authors: McAlpine J. F.
Published: January 2010

The discovery of a new species of Herina Desv. [=Tephronota Loew] has provided the opportunity of reviewing the genus in North America. In the following discussion, which includes a description of the new species and a key to the four recognized Nearctic species, I also present notes on nomenclature, distribution, and relationships between species.
A Toxicological and Histophysiological Study of Certain New Insecticides as “Stomach Poisons” to the Honey BeeApis melliferaL.
Authors: Salkeld E. H.
Published: January 2010

The Effect of DDT on the Mid-Gut of the Bee

The mid-gut from twelve bees poisoned with the pure para isomer of DDT was studied. Of these, five contained the large bubble of gas described on page 48: their histological appearance was almost identical but it differed in some ways from those which contained no bubble.
The Role of the Ant in the Biological Control of Homopterous Insects
Authors: Flanders Stanley E.
Published: January 2010

The ant as a factor in “facultative helotism” plays an important role in the biological conrrol of certain agricultural pests. This phenomenon was noted by Linnè in 1758 (Jones 1929; Wheeler 1910), when he observed that honeydew-producing insects such as aphids, mealybugs, and scale insects often functioned as “cows of the ants.”

The importance of this function in the biological control of homopteroas insects lies in the fact that certain species are effectively controlled by their natural enemies when ants are absent, but not when ants are present. The ant, in gathering the honeydew supplied by such homopterous insects, tends more or less automatically to protect them from their natural enemies (Huber 1810). This apparently protective effect is not limited to the honeydew-producing species hut is often extended to other phytophagous forms such as the citrus red mite,Paratetranychus citri(McGregor), (Kenyon 1935; DeBach, Fleschner, and Dietrick 1951) and diaspid scale insects (Flanders 1945) when such forms happen to be within the area of ant activity.
Observations on the Biology and Control of Pest Trichoptera at Fort Erie, Ontario
Authors: Peterson D. G.
Published: January 2010

The community of Fort Erie, Ontario, and the waterfront zone of Buffalo, New York, form one of the many areas in the St. Lawrence River drainage system that are annually infested by large numbers of adult Trichoptera and, to a lesser degree, Ephemerida. Betten (1934) reported on a field study, conducted in 1906, of the Trichoptera found at Buffalo, N.Y. He noted the prevalent species and the extent of the problem chat the insects create for the local inhabitants. The medical aspect was investigated by Parlato (1929, 1930, 1932) and Osgood (1934). In August, 1950, an investigation of the scale, composition, and source of the trichopteran infestation and possible control measures was initiated at Fort Erie, Ontario.
Key to the Puparia of the Dipterous Parasites of Choristoneura fumiferana Clem.
Authors: Ross D. A.
Published: January 2010

The frequent failure of parasite development beyong the immature stages during insectary rearing work often results in incomplete qualitative and quantitative data on insect parasites. Keys to the larval and pupal stages are therefore an extremely useful aid in completing the picture in a study of A parasite complex.

The following illustrated key makes it feasible to obtain reasonably accurate specific determinations of the puparia of the dipterous parasites of the spruce budworm, Choristoneura fumiferana Clem., that occur in Canada. The writer gratefully acknowledges the inspiration and co-operation of A. R. Brooks during the preliminary preparations for the key. The illustrations were executed by Miss M. MacKay (Figs. 1-14) and R. Sugden (Fig. 15). Each figure illustratis the following: (a) posterior aspect of a puparium showing the location of the stigmal plates and the anal aperture, and any protuberances that are present; (b) one stigmal place and the stigmal slits; (c) lateral aspect of the outline of a puparium.
Chlamisus sp. (Coleoptera: Chrysomelidae), a New Pest of Strawberries
Authors: Morgan G. T. , Maxwell C. W.
Published: January 2010

In July, 1949, a single specimen of a casebearing coleopterous larva was found feeding on a strawberry leaf in a plantation at the southeastern end of Grand Lake, Queen's County, N.B. During June and July, 1950, about a dozen larvae were found throughdut this area, and a greater number in plantations on both sides of Washademoak Lake, which is southeast and roughly parallel to Grand Lake and about ten miles distant. During 1951 the species was again collected in these areas, and was found in large numbers about 15 miles southeast of Washademoak Lake in the Belleisle watershed. Here the infestation was so great that in one instance 565 larvae were collected with a sweeping net on 100 feet of strawberry row, or an average of five larvae per plant.
A Study of Insecticide Resistance in Strains of Drosophila melanogaster Meig.
Authors: Bartlett Blair R.
Published: January 2010

The development of strains or races of insects that are resistant to insecticides is a serious obstacle to the progress of chemical pest control. In many cases recommendations at first viewed as offering a permanent solution for an entomological problem have had to be abandoned within a very few years. Until the general relationships governing insccticidnl resistance are reduced to an orderly and understandable basis, the permanent soIution nf an insect pest control problem by chemical treatment is largelv an unjustifiable expectation.
Mallophaga Collected from Birds in Ontario
Authors: Stirrett Geo. M.
Published: January 2010

It is difficult to obtain accurate records of the occurrence of bird-lice and especially those associating them with correctly identified hosts. For this reason it is considered the following records of bird-lice, taken from birds in Ontario, may be of interest and should be published.

The collections were made by the author and Messrs. A. A. Wood and D. A. Arnott and one or two other persons. The specimens are in the collection of the Dominion Entomological Laboratory, Chatham, Ontario.
Circumpolar Distribution of Water Boatmen (Hemiptera: Corixidae)
Authors: Sailer R. I.
Published: January 2010

Only two species of Corixidae, commonly known as water boatmen, are known to occur in both the Old and New Worlds. One of these is Callicorixa producta Reuter, which Hungerford (1948) has divided into three subspecies. On the basis of existing records the typical subspecies is restricted to the Scandinavian peninsula and Finland. The second subspecies, producta sackalinensis (Matsumura), is so far known only from northern Manchuria and Sakhalin Island. The third subspecies, producta noorvikensis Hungerford, appears to straddle the Rering Sea, specimens being recorded from near Kolyma River in Siberia and from Bering Island in the Komandorskies east across Alaska and Northwest Territories to Hudson Bay.
Adult Mosquito Control by Airspray in Northern British Columbia and the Yukon
Authors: Sharp J. F.
Published: January 2010

Experimental aerial spraying to control mosquitoes was carried out in 1949 and 1950 at several stations of the Royal Canadian Air Force in northern Canada. An account of the work in 1949 has been presented (Twinn, Brown, and Hurtig, 1950). The experiments in 1949 involved the use of a larvicide, followed by a spray against the adults. Further data were required on the degree of effective control that could be obtained by applying one or two sprays against the adult mosquitoes only, in plots of reasonable size. Consequently, in 1950, arrangements were made with the R.C.A.F. to carry out airspray operations against adult mosquitoes at four stations in the Northwest as follows: Fort Nelson, B.C., 24 sq. mi. in two operations, June 6-8 and 19-20; Whitehorse, Y.T., 22 sq. mi. in two operations, June 13-15 and June 30-July 1; Watson Lake, Y.T., 12 sq. mi. June 21-22; and Norman Wells, N.W.T., 8 sq. mi. June 28-29.
TheIllibalisGroup of the GenusPalpitaHübner (Lepidoptera: Pyralidae)
Authors: Munroe Eugene
Published: January 2010

For many years the true members of theillibalisgroup (usually placed in the wastebasket genusPyrausta) have been listed as two or three species, under the namesgracilalisHulst,illibalisHübner, andarsalteulisWalker. I was considerably surprised, therefore, to find several additional species standing, for the most part unrecognized, in North American collections. A further species,haedulalisHulst, was compared by its author togracilalis, and was placed by McDunnough (1939) betweengracilalisandillibalis; I have seen the badly damaged tvpe ofhaedulalisin the collection of Rutgers University, and am convinced ihat the species does not belong in the present group.
Notes on the Stages and the Biology ofBaryodma ontarionisCasey (Coleoptera: Staphylinidae), a Parasite of the Cabbage Maggot,Hylemya brassicaeBouché (Diptera: Anthomyiidae)
Authors: Colhoun E. H.
Published: January 2010

During investigations on the natural enemies of root maggots attacking Cruciferae, the beetleBaryodma ontarionisCasey was reared from puparia of the cabbage maggot,Hylemya brassicae(Bouché). This was not unexpected, for Gibson and Treherne (1916) had reported a similar occurrence; the staphylinid beetles reared at that time were identified by Casey (1916), who decided that they belonged to thevernagroup ofBaryodmaand assigned the nameBaryodma ontarionis. Casey (loc. cit.) considered the species rather common and stated that it did not seem to resemble any European species; but Mr. W. J. Brown (in litt.), Systematic Entomology, Division of Entomology, Ottawa, who identified the beetles collected in 1950, is of the opinion thatB. ontarionisis synonymous withAleochara bilineataGyll., tvhich attaclrs the cabbage maggot in Europe. Wadsworth (1915) dealt with the biology ofA. bilineata, giving detailed descriptions of the immature stages. A study of the biology ofB. ontarioniswas carried out at the Belleville laboratory as part of n program of parasite introduction with the purpose in view of using the information to evaluate the beetle as a factor in the control of root maggots that are severe pests of cabbage, cauliflower, turnip, and radish.
A New Zygethopolys from Kentucky and a Key to the Members of the Genus. (Chilopoda: Lithobiomorpha: Lithobiidae: Ethopolyinae)
Authors: Crabill Ralph E.
Published: January 2010

Almost all of the members of the subfamily Ethopolyinae occur in western North America, a few Pacific islands, the Orient and Europe, but only one established species had been known from North America east of the Rocky Mountains. This widespread and very common form, Bothropolys multidentatus (Newport), ranges throughout the East as far west as Missouri. The present new species is therefore of special interest in that it is the second endemic member of the subfamily to he recorded from east of the Rockies. The only other members of Zygethopolys, a genus closely allied to Bothropolys, are known only from Alaska, British Columbia, and thk state of Washington.
The Spruce Budworm, Choristoneura fumiferana (Clem.) and an Allied New Species on Pine (Lepidoptera: Tortricidae)
Authors: Freeman T. N.
Published: January 2010

This paper has been extracted mainly from the manuscript of a revision of the tortricid subfamily Archipinae, to make available a scientific name for an injurious, undescribed Choristoneura species that feeds in the larval stage upon pines, particularly jack pine, Pinkus banksiana Lamb., and red pine, P. resinosa Ait. This insect and the closely allied Choristorneura fumiferana Clem. are compared under the following topics: taxonomic history, maculation, morphology, and distribution. References are cited only if they contain information of taxonomic significance; the vast amount of economic literature dealing with these species has been omitted. This paper is followed by a comparative study of the larvae of the two species by Miss M. MacKay, by one by Miss C. E. Cox on the mathematical significance of the anatomical differences in the larvae and adults of both species, by a discussion of some of the parasites of the pine species by G. S. Walley, and by a discussion by S. G. Smith of the isolating mechanisms aperating between the two species.
The Larvae ofChoristoneura fumiferana(Clem.) andC.pinusFree. (Lepidoptera: Tortricidae)
Authors: MacKay Margaret R.
Published: January 2010

It has long been known that a series of late-instar larvae ofChoristoneura fumiferana(Clem.) may be distinguished from one ofC. pinusFree. by colour differences of the head and prothoracic shield: specimens of the former usually have dark heads and light prothoracic shields; specimens of the latter usually have light heads and dark prothoracic shields. However, intensive study of the larvae, including numerous specimens ofC. fumiferanafrom the spruce-balsam fir areas of Algonquin Park, Ontario, and ofC. pinusfrom jack-pine areas at Normandale, Ontario, has shown that there are highly significant structural differences in the head; these differences serve to identify small series of either species and most single specimens.
Chauliodes disjunctus Walker: a Correction, with the Descriptions of a New Species and a New Genus (Megaloptera: Corydalidae)
Authors: Munroe E. G.
Published: January 2010

Shirtly after the appearance of my earlier paper (Munroe, 1951) on Chauliodes disjunctus, Prof. G. J. Spencer, of the University of British Columbia, wrote to me that he had two kinds of chauliodine males, one agreeing with what I described as the male of disjunctus, and another which he considered to be the true male of that species.
Observations on Internal Parasites (Hymenoptera: Scelionidae) of Eggs of Pest Grasshopper Species in the Prairie Provinces of Canada
Authors: Putnam L. G.
Published: January 2010

Internal parasites belonging to the genus Scelio Latr. have been reported found in grasshopper eggs in several of the northern states of the United States. Muesebeck and Walkley (1951, p. 702) reported S. calopteni Riley in Melanoplus spp., including M. mexicanus mexicanus (Sauss.) and M. bivittatus (Say), in states adjacent to thc Prairie Provinces of Canada. In Canada, Criddle (1921) reported Scelio sp(p). in Manitoba during a grasshopper outbreak which took place about 1920. Since then, the presence of Scelio sp(p). in grasshopper eggs has frequently been noted in the Prairie Provinces by entomologists. Studies of the viability, embryonic development, and parasitism of Western Canadian grasshopper eggs begun and largely carried out by the late Mr. H. W. Moore at the Field Crop Insect laboratories at Brandon and Saskatoon have made possible an approach to the quantitative evaluation of these parasites.
Psithyrus insularis (Sm.) in a Nest of Bombus ternarius Say (Hymenoptera: Bombidae)
Authors: Craig C. H.
Published: January 2010

Franklin (1913) (p. 448) stated, “There is not vet a single new world account of a Psithyrus having been found in a Bombus nest”. Since then, of the seven North American species, four have been reported found in nests of Bombus spp. by Sladen (1915), Frison (1916, 1921, 1926), Plath (1934), Linsley (1944), and Leech (1947). Of these records only two are from Canada, both being from British Columbia. Sladen (1915) reported finding the well-preserved body of a female of Psithyrus insularis (Sm.) and several cocoons, from one of which he extracted a male of P. insularis, in a nest containing an old queen and several workers of Bombus flavifrons Cress. Leech (1947) found a P. insularis female in a nest containing several workers of Bombus mixtus Cress., and concluded that the iniquiline had supplanted the mixtus queen.
Notes on the Life History and Seasonal Development of the Pine Needle Scale, Phenacaspis pinifoliae (Fitch) (Diaspididae: Homoptera)
Authors: Cumming Margaret E. P.
Published: January 2010

The pine needle scale is a serious pest of spruce and pine in shelter-belt and ornamental plantings in the agricultural region of the Prairie Provinces of Canada. The present study was made to provide accurate data on the life cycle, habits, and seasonal development of the pine needle scale in this region. This information is essential for investigations of artificial control.

Observations were made at Indian Head, Sask., in 1947. The populations sampled were on Scotch pine in a shelter belt and white spruce in an ornamental planting. Other populations were sampled when further information was required.
Observations on Mosquitoes at Whitehorse, Yukon Territory (Culicidae: Diptera)
Authors: Curtis L. Colin
Published: January 2010

During the summers of 1949 and 1950, studies on the biology of mosquitoes were carried out at Whitehorse, Y.T.

At Whitehorse, the principal area under study centred about the Royal Canadian Air Force Station. Some additional collections were made along the Northwest Staging Route, at Fort St. John and Fort Nelson, B.C., and Watson
Lake, Y.T.
Some Micro-organisms Associated with the Weevils Sitophilus granarius (L) and Sitophilus oryza (L).: I Distribution and Description of the Organisms
Authors: Musgrave A. J. , Miller J. J.
Published: January 2010

It has been generally accepted by insect microbiologists and physiologists that many insects harbour beneficial micro-organisms. The contributions of Buchner (1933), Glaser (1946), Jeanne1 (1949), Steinhaus (1946), Wigglesworth (1950) and Woodward (1949) are relevant. Some experimental evidence has been contributed by Aschner 1935, Blewett and Fraenkel (1944), and Brecher and Wigglesworth (1944). It seems that the micro-organisms may sometimes supply the host with vitamins of the B group. (Blewett and Fraenkel). Many species of insects have special organs, called mycetomes, whose chief function seems to be the housing of micro-organisms. Furthermore it has been suggested that special arrangements exist for the transference of micro-organisms from one generation of insects to the next. (Mansour, 1935; Murray and Tiegs, 1935; and Woodward 1949).
The Protocephalon: A Critique of Recent Interpretations
Authors: DuPorte E. Melville
Published: January 2010

The term “protocephalon” as used by Snodgrass (1938) applies to that portion of the head which lies anterior to the mandibular segment. As defined by him it is composed of the “prostomial acron” and a postantennal segment. The term “acron” has been used in somewhat different senses by different authors and to avoid confusion I have introduced the term “blastocephalon” instead. The blastocephalon may be defined as that portion of the head which includes the labrum, clypeus and occulo-antenna1 region. In the germ band it appears as an expanded anterior region, the cephalic lobes, which forms a sort of early embryonic head, hence the name. The posterior trunk-like region of the germ band may then be called the blastocorm.
Effects of the Destruction of the Current Year's Foliage of Balsam Fir on the Fecundity and Habits of Flight of the Spruce Budworm
Authors: Blais J. R.
Published: January 2010

When spruce budworm larvae emerge in the spring, they either mine the needles of old foliage or feed upon the freshly opened staminate flowers of balsam fir. As soon as the vegetative buds begin to expand, the larvae abandon the needle mines for this newer and more succulent growth. Later, when the pollen is shed, the staminate flowers are in turn abandoned in favour of new shoots. Usually, the larvae continue to feed on the new shoots until pupation. When this insect reaches epidemic proportions, however, the current year's growth is often totally destroyed prior to the completion of the larval stage. Late spring frosts have also been known to destroy, in part, or even completely, the shoots of the current year's growth. Under these conditions spruce budworm larvae must resort to feeding on old foliage.
Polythene-stoppered Vials for Storing Insects in Alcohol
Authors: Strickland E. H.
Published: January 2010

Many attempts have been made to overcome the difficulties attendant upon storing insect material over extended periods of time in small vials of alcohol. Cork stoppers fail to meet requirements for various reasons, while their substitution with rubber ones may introduce still further complications. Both are liable to shrink or to swell while either may be forced out of the vials as a result of variations in room temperature. In addition, neither can be readily marked in such a manner that the contents of the vials are permanently and plainly legible from above.
Rapid Method for Mounting Nematodes in Glycerine
Authors: Baker A. D.
Published: January 2010

The prevailing method of preparing glycerine mounts of nematodes consists essentially of transferring the specimens from the fixative to 1.5-2.0 per cent glycerine in water and then allowing the water to evaporate very slowly until the nematodes are in pure glycerine. By this method evaporation is completed in not less than four weeks as any attempt to hurry this process will distort the specimens. A desiccator is used to complete the removal of the water from the glycerine.
Note on Preliminary Field Trials of a Bacterium to Control the Codling Moth
Authors: Phillips C. M. , Bucher Gordon E. , Stephens June M.
Published: January 2010

A bacterium, Bacillus cereus F. and F., which was isolated from diseased larvae of the codling moth, Carpocapsa pomonella (L.), is pathogenic to the codling moth in laboratory experiments (Stephens, 1952).

A series of trials was set up at Kentville to test the effectiveness of this bacterium against codling moth larvae in the field. B. cereus spores were propagated according to the method of Reed and McKercher (1948) and shipped to the field as spore suspensions.
Mast Cells, Histamine, and IL-6 Regulate the Selective Influx of Dendritic Cell Subsets into an Inflamed Lymph Node
Authors: Dawicki Wojciech , Jawdat Dunia W. , Xu Nong , Marshall Jean S.
Published: January 2010

In response to bacterial stimuli, multiple dendritic cell (DC) populations accumulate within the draining lymph node, thus enhancing opportunities for effective T cell–DC interaction. DC subpopulations, such as plasmacytoid, CD8+, and CD11b+ subsets, have distinct roles in determining the nature of the immune response. The mechanisms whereby individual DC subpopulations are mobilized and the extent to which these processes are linked to increases in overall lymph node cellularity have not been determined. In the current study, the mechanisms of DC subset mobilization to the draining auricular lymph node were examined after intradermal injection of Staphylococcus aureus-derived peptidoglycan. Using mast cell-deficient mice and local mast cell reconstitution, plasmacytoid and CD8+ DC responses were shown to be mast cell dependent, whereas the CD11b+ DC response was not. A histamine H2 receptor-dependent, CXCL9-independent pathway controlled the selective influx of both plasmacytoid and CD11b+ DC into the lymph node, but not lymph node cellularity. In contrast, IL-6 was important for the mobilization of CD8+ and CD11b+ DC. TNF and IL-1 receptor were dispensable for plasmacytoid, CD11b+, and CD8+ DC responses. These findings provide novel opportunities for the selective mobilization of specific DC subsets to lymph nodes and demonstrate critical roles for both histamine and IL-6 in this process.
Myelin Basic Protein Priming Reduces the Expression of Foxp3 in T Cells via Nitric Oxide
Authors: Brahmachari Saurav , Pahan Kalipada
Published: January 2010

Regulatory T cells (Tregs) play a vital role in autoimmune disorders. Among several markers, forkhead box p3 (Foxp3) is the most specific with regard to Treg activity. Therefore, understanding mechanisms that regulate Foxp3 expression is a critical step for unraveling the complicacy of autoimmune pathophysiology. The present study was undertaken to investigate the crosstalk between NO and Tregs. Interestingly, after myelin basic protein (MBP) priming, the expression of Foxp3 decreased in MBP-primed T cells. However, blocking NO either by inhibiting inducible NO synthase with l-N6-(1-iminoethyl)-lysine hydrochloride or through scavenging with PTIO or by pharmacological drugs, such as pravastatin, sodium benzoate, or gemfibrozil, restored the expression of Foxp3 in MBP-primed T cells. However, this restoration of Foxp3 by pharmacological drugs was reversed by S-nitrosoglutathione, an NO donor. Similarly, NO also decreased the populations of Tregs characterized by CD4+CD25+ and CD25+FoxP3+ phenotypes. We have further confirmed this inverse relationship between NO and Foxp3 by analyzing the mRNA expression of Foxp3 and characterizing CD25+FoxP3+ or CD4+Foxp3+ phenotypes from inducible NO synthase knockout mice. Moreover, this inverse relation between NO and Foxp3 also was observed during priming with myelin oligodendrocyte glycoprotein, another target neuroantigen in multiple sclerosis, as well as collagen, a target autoantigen in rheumatoid arthritis. Finally, we demonstrate that NO inhibited the expression of Foxp3 in MBP-primed T cells via soluble guanylyl cyclase-mediated production of cGMP. Taken together, our data imply a novel role of NO in suppressing Foxp3+ Tregs via the soluble guanylyl cyclase pathway.
Influenza Virus-Specific Immunological Memory Is Enhanced by Repeated Social Defeat
Authors: Mays Jacqueline W. , Bailey Michael T. , Hunzeker John T. , Powell Nicole D. , Papenfuss Tracey , Karlsson Erik A. , Padgett David A. , Sheridan John F.
Published: January 2010

Immunological memory (MEM) development is affected by stress-induced neuroendocrine mediators. Current knowledge about how a behavioral interaction, such as social defeat, alters the development of adaptive immunity, and MEM is incomplete. In this study, the experience of social disruption stress (SDR) prior to a primary influenza viral infection enhanced the frequency and function of the T cell memory pool. Socially stressed mice had a significantly enlarged population of CD8+ T cells specific for the immunodominant NP366–74 epitope of A/PR/8/34 virus in lung and spleen tissues at 6–12 wk after primary infection (resting memory). Moreover, during resting memory, SDR-MEM mice responded with an enhanced footpad delayed-type hypersensitivity response, and more IFN-γ–producing CD4+ T cells were detected after ex vivo stimulation. When mice were rechallenged with A/PR/8/34 virus, SDR-MEM mice terminated viral gene expression significantly earlier than MEM mice and generated a greater DbNP366–74CD8+ T cell response in the lung parenchyma and airways. This enhancement was specific to the T cell response. SDR-MEM mice had significantly attenuated anti-influenza IgG titers during resting memory. Similar experiments in which mice were primed with X-31 influenza and challenged with A/PR/8/34 virus elicited similar enhancements in the splenic and lung airway DbNP366–74CD8+ T cell populations in SDR-MEM mice. This study demonstrates that the experience of repeated social defeat prior to a primary viral infection significantly enhances virus-specific memory via augmentation of memory T cell populations and suggests that social stressors should be carefully considered in the design and analysis of future studies on antiviral immunity.
Loss of CD4+ T Cell IL-6R Expression during Inflammation Underlines a Role for IL-6TransSignaling in the Local Maintenance of Th17 Cells
Authors: Jones Gareth W. , McLoughlin Rachel M. , Hammond Victoria J. , Parker Clare R. , Williams John D. , Malhotra Raj , Scheller Jürgen , Williams Anwen S. , Rose-John Stefan , Topley Nicholas , Jones Simon A.
Published: January 2010

IL-6 responses are classically orchestrated via a membrane-bound IL-6R (CD126) α subunit (classical IL-6R signaling) or through a soluble form of this cognate receptor (IL-6 trans signaling). Appraisal of IL-6R expression on human and mouse T cells emphasized that IL-6R expression is closely linked with that of CCR7 and CD62L. In this regard, infiltrating effector T cells from clinical and experimental peritonitis episodes lose IL-6R expression, and anti-CD3/CD28 Ab costimulation of peripheral T cells in vitro leads to a downregulation in IL-6R expression. Consequently, IL-6 signaling through membrane-bound IL-6R seems to be limited to naive or central memory T cell populations. Loss of IL-6R expression by activated T cells further suggests that these effector cells might still retain IL-6 responsiveness via IL-6 trans signaling. Using IL-6R–deficient mice and recombinant tools that modulate the capacity of IL-6 to signal via its soluble receptor, we report that local control of IL-6 trans signaling regulates the effector characteristics of the T cell infiltrate and promotes the maintenance of IL-17A–secreting CD4+ T cells. Therefore, we concluded that classical IL-6R signaling in naive or central memory CD4+ T cells is required to steer their effector characteristics, whereas local regulation of soluble IL-6R activity might serve to maintain the cytokine profile of the Th cell infiltrate. Therefore, the activation status of a T cell population is linked with an alteration in IL-6 responsiveness.
IL-6 Promotes NK Cell Production of IL-17 during Toxoplasmosis
Authors: Passos Sara T. , Silver Jonathan S. , O’Hara Aisling C. , Sehy David , Stumhofer Jason S. , Hunter Christopher A.
Published: January 2010

Previous studies have implicated T cell production of IL-17 in resistance to Toxoplasma gondii as well as the development of immune-mediated pathology during this infection. Analysis of C57BL/6 and C57BL/6 RAG−/− mice challenged with T. gondii-identified NK cells as a major innate source of IL-17. The ability of soluble Toxoplasma Ag to stimulate NK cells to produce IL-17 was dependent on the presence of accessory cells and the production of IL-6, IL-23, and TGF-β. In contrast, these events were inhibited by IL-2, IL-15, and IL-27. Given that IL-6 was one of the most potent enhancers of NK cell production of IL-17, further studies revealed that only a subset of NK cells expressed both chains of the IL-6R, IL-6 upregulated expression of the Th17-associated transcription factor RORγt, and that IL-6−/− mice challenged with T. gondii had a major defect in NK cell production of IL-17. Together, these data indicate that many of the same cytokines that regulate Th17 cells are part of a conserved pathway that also control innate production of IL-17 and identify a major role for IL-6 in the regulation of NK cell responses.
Critical Role of the IFN-Stimulated Gene Factor 3 Complex in TLR-Mediated IL-27p28 Gene Expression Revealing a Two-Step Activation Process
Authors: Molle Céline , Goldman Michel , Goriely Stanislas
Published: January 2010

In myeloid dendritic cells, activation of the IL-27p28 gene is selectively induced by ligands of TLR4 or TLR3, both coupled to the Toll/IL-1R–related domain-containing adaptor-inducing IFN/IFN regulatory factor (IRF)3 pathway. In response to both ligands, autocrine type 1 IFN production was required for optimal IL-27p28 expression. Type I IFN signaling was necessary for sustained IRF1 activation and formation of the IRF9-containing IFN-stimulated gene factor 3 complex. Indeed, we demonstrated that IRF1 and IRF9 are sequentially activated and recruited to the IL-27p28 IFN-stimulated regulatory element site. Involvement of IRF1 and IRF9 in the induction of IL-27p28 was confirmed in vitro and upon in vivo exposure to TLR ligands. Thus, in response to TLR4 or TLR3 ligation, the initial induction of the IL-27p28 gene depends on the recruitment of IRF1 and IRF3, whereas transcriptional amplification requires recruitment of the IFN-stimulated gene factor 3 complex. These results highlight the complex molecular interplay between TLRs and type I IFNs for the control of IL-27 synthesis.
Cyclophosphamide Induces Dynamic Alterations in the Host Microenvironments Resulting in a Flt3 Ligand-Dependent Expansion of Dendritic Cells
Authors: Salem Mohamed L. , AL-Khami Amir A. , EL-Naggar Sabry A. , Díaz-Montero C. Marcela , Chen Yian , Cole David J.
Published: January 2010

Preconditioning a recipient host with lymphodepletion can markedly augment adoptive T cell therapy. However, the precise mechanisms involved are poorly understood. In a recent study, we observed a significant increase in the circulating levels of dendritic cells (DCs; CD11c+CD11b+) during the recovery from cyclophosphamide (CTX)-induced lymphodepletion. Herein, we demonstrate that the CTX-induced DC expansion was not altered by adjuvant chemotherapy or tumor burden but was augmented by coadministration of granulocyte-colony stimulating factor. Although the increase in the number of DCs was preceded by a systemic expansion of a population expressing the phenotype of myeloid-derived suppressor cells (Gr-1+CD11b+), depletion of these Gr-1+ cells had no effect on the noted expansion. Moreover, when Gr-1highCD11bhigh cells were sorted from CTX-treated mice and adoptively transferred into control or CTX-treated recipients, they did not differentiate into DCs. Post-CTX expansion of DCs was associated with proliferation of DCs in bone marrow (BM) during the lymphopenic phase and in the blood and spleen during the recovery phase. Furthermore, adoptive transfer of BM cells from CTX-treated mice produced equal numbers of DCs in the blood of either CTX-treated or untreated recipients. CTX induced a dynamic surge in the expression of growth factors and chemokines in BM, where CCR2 and Flt3 signaling pathways were critical for DC expansion. In sum, our data suggest that CTX induces proliferation of DCs in BM prior to their expansion in the periphery. Targeting DCs at these phases would significantly improve their contribution to the clinical application of lymphodepletion to adoptive immunotherapy.
Dendritic Cells Support Homeostatic Expansion of Foxp3+ Regulatory T Cells in Foxp3.LuciDTR Mice
Authors: Suffner Janine , Hochweller Kristin , Kühnle Marie-Cristine , Li Xingrui , Kroczek Richard A. , Garbi Natalio , Hämmerling Günter J.
Published: January 2010

Foxp3+CD4+ regulatory T cells (Tregs) are crucial in maintaining self-tolerance and limiting immune responses to pathogens. Shifting the sensitive balance between Tregs and effector T cells requires extensive knowledge of the homeostatic properties of the different T cell populations. For the investigation of Treg homeostatic expansion, we introduce in this study novel BAC transgenic mice, designated Foxp3.LuciDTR, coexpressing enhanced GFP, luciferase for bioluminescence imaging of Tregs, and the diphtheria toxin receptor (DTR) for specific ablation of Tregs. Of several founder lines, Foxp3.LuciDTR-4 mice displayed ∼95% Treg depletion following injection of DT, resulting in activation of conventional CD4+ T cells, probably due to lack of control by Tregs. In contrast, Foxp3.LuciDTR-3 mice displayed only ∼70% Treg depletion without concomitant activation of CD4+ T cells and represented, therefore, a suitable model to study Treg homeostasis in an environment where other T cell populations were not altered. After depletion, the Treg compartment recovered to its original size in ∼2 wk. This recovery was mediated in a thymus-independent fashion by homeostatic proliferation of the surviving, nondepleted Tregs. The proliferating Tregs acquired an activated phenotype and maintained their suppressive capacity. Studies involving DT-mediated depletion of dendritic cells in CD11c.DOG mice showed that dendritic cells were required for optimal Treg homeostasis. In addition, IL-2 was identified as an essential factor for homeostatic recovery of the Treg compartment. These results show that Treg homeostasis is specifically regulated by the size of the Treg compartment and is independent of proliferation of conventional T cells.
IL-23 Receptor Regulates Unconventional IL-17–Producing T Cells That Control Bacterial Infections
Authors: Riol-Blanco Lorena , Lazarevic Vanja , Awasthi Amit , Mitsdoerffer Meike , Wilson Brian S. , Croxford Andy , Waisman Ari , Kuchroo Vijay K. , Glimcher Laurie H. , Oukka Mohamed
Published: January 2010

IL-23 plays an important role in autoimmune tissue inflammation and induces the generation of not fully characterized effector cells that mediate protection against pathogens. In this paper, we established the essential role of IL-23R in the host response against intracellular pathogens. IL-23 was critical for the expansion or maintenance of γδ and double negative (DN) αβ T cells. These cells were rapidly recruited to the site of infection and produced large amounts of IL-17, IFN-γ, and TNF-α. Notably, DN T cells transferred into L. monocytogenes-infected RAG2−/− mice prevented bacterial growth, confirming their protective role against intracellular pathogens. Our results show that IL-23 regulates the function of IL-17–producing γδ and DN T cells, two essential components of the early protective immune response directed against intracellular pathogens.
Mutational Analyses Reveal that the Staphylococcal Immune Evasion Molecule Sbi and Complement Receptor 2 (CR2) Share Overlapping Contact Residues on C3d: Implications for the Controversy Regarding the CR2/C3d Cocrystal Structure
Authors: Isenman David E. , Leung Elisa , Mackay Julia D. , Bagby Stefan , van den Elsen Jean M. H.
Published: January 2010

We recently characterized an interaction between the Staphylococcus aureus immune evasion molecule Staphylococcus aureus binder of Ig (Sbi) and complement C3, an interaction mediated primarily through the binding of C3d(g) to Sbi domain IV. Events related to these studies prompted us to investigate via mutagenesis the binding interface of C3d for Sbi domain IV (Sbi-IV), as well as to revisit the controversial issue of the complement receptor 2 (CR2) binding site of C3d. Specifically, we had shown that Sbi domains III and IV fragment binding to C3dg inhibited the latter’s binding to CR2. Moreover, a published cocrystal structure of C3d bound to complement inhibitory C-terminal domain of extracellular fibrinogen-binding protein (Efb-C), a structural and functional homolog of Sbi-IV, showed Efb-C binding to a region on the concave face of C3d previously implicated in CR2 binding by our mutagenesis data but not confirmed in the CR2(short consensus repeat [SCR]1–2):C3d cocrystal structure. We have now analyzed by surface plasmon resonance the binding of a series of variant C3dg molecules to biosensor-bound Sbi-IV or CR2(SCR1–2). We found that mutations to the concave face acidic pocket of C3d significantly affected binding to both Sbi-IV and CR2, although there was divergence in which residues were most important in each case. By contrast, no binding defects were seen for mutations made to the sideface of C3d implicated from the cocrystal structure to be involved in binding CR2(SCR1–2). The results with Sbi-IV suggest a mode of binding highly similar to that visualized in the Efb-C:C3d complex. The results with CR2 confirm our earlier mapping studies and cast even further doubt on the physiologic relevance of the complex visualized in the C3d:CR2 cocrystal.
T Cell/Transmembrane, Ig, and Mucin-3 Allelic Variants Differentially Recognize Phosphatidylserine and Mediate Phagocytosis of Apoptotic Cells
Authors: DeKruyff Rosemarie H. , Bu Xia , Ballesteros Angela , Santiago César , Chim Yee-Ling E. , Lee Hyun-Hee , Karisola Piia , Pichavant Muriel , Kaplan Gerardo G. , Umetsu Dale T. , Freeman Gordon J. , Casasnovas José M.
Published: January 2010

T cell/transmembrane, Ig, and mucin (TIM) proteins, identified using a congenic mouse model of asthma, critically regulate innate and adaptive immunity. TIM-1 and TIM-4 are receptors for phosphatidylserine (PtdSer), exposed on the surfaces of apoptotic cells. Herein, we show with structural and biological studies that TIM-3 is also a receptor for PtdSer that binds in a pocket on the N-terminal IgV domain in coordination with a calcium ion. The TIM-3/PtdSer structure is similar to that of TIM-4/PtdSer, reflecting a conserved PtdSer binding mode by TIM family members. Fibroblastic cells expressing mouse or human TIM-3 bound and phagocytosed apoptotic cells, with the BALB/c allelic variant of mouse TIM-3 showing a higher capacity than the congenic C.D2 Es-Hba–allelic variant. These functional differences were due to structural differences in the BC loop of the IgV domain of the TIM-3 polymorphic variants. In contrast to fibroblastic cells, T or B cells expressing TIM-3 formed conjugates with but failed to engulf apoptotic cells. Together these findings indicate that TIM-3–expressing cells can respond to apoptotic cells, but the consequence of TIM-3 engagement of PtdSer depends on the polymorphic variants of and type of cell expressing TIM-3. These findings establish a new paradigm for TIM proteins as PtdSer receptors and unify the function of the TIM gene family, which has been associated with asthma and autoimmunity and shown to modulate peripheral tolerance.