bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose-Dependent Activation of Lymphocytes in Endotoxin-Induced Airway Inflammation
Authors: Larsson Roland , Rocksén David , Lilliehöök Bo , Jonsson Åsa , Bucht Anders 
Published: July 2002

ABSTRACTRecruitment of neutrophils to lung tissue and airspaces is a hallmark of inflammatory events following inhalation of endotoxins. We studied the role of different lymphocyte subsets in this inflammation, which is assumed to primarily involve the innate immune system. Inhalation of aerosolizedEscherichia colilipopolysaccharide (LPS) in mice induced a dose-dependent increase in neutrophils in bronchoalveolar lavage fluid, reaching a maximum after 12 h at a low dose and after 24 h at a high dose. Profiles of gene expression in lung tissue indicated an early (2 h) and transient onset of proinflammatory cytokines and chemokines by a low dose of LPS, while a high dose caused more delayed and sustained (6 to 12 h) activation. Gamma interferon, interleukin-2 (IL-2), RANTES, and the α chain of the IL-2 receptor were not expressed at a low dose, whereas a high dose of LPS induced a strong expression of these genes, indicating a dose-dependent activation of T cells. A similar pattern was observed for IL-17, supporting a contribution of T cells to the neutrophilic inflammation only at high-dose exposure to LPS. The involvement of lymphocytes in the inflammatory response was further studied using mice with functional deficiencies in defined lymphocyte subsets. Both γδ T-cell- and B-cell-deficient mice displayed a response similar to that of the corresponding wild-type strains. Selective depletion of NK cells by in vivo administration of the pk136 antibody did not significantly affect the recruitment of neutrophils into airspaces. Thus, neither NK cells, B cells, nor γδ T cells appeared to participate in the host response, suggesting that among the lymphocyte subsets, αβ T cells are exclusively involved in endotoxin-induced airway inflammation.
Cleavage of a Recombinant Human Immunoglobulin A2 (IgA2)-IgA1 Hybrid Antibody by Certain Bacterial IgA1 Proteases
Authors: Senior Bernard W. , Dunlop James I. , Batten Margaret R. , Kilian Mogens , Woof Jenny M. 
Published: July 2002

ABSTRACTTo understand more about the factors influencing the cleavage of immunoglobulin A1 (IgA1) by microbial IgA1 proteases, a recombinant human IgA2/IgA1 hybrid molecule was generated. In the hybrid, termed IgA2/A1 half hinge, a seven-amino-acid sequence corresponding to one half of the duplicated sequence making up the IgA1 hinge was incorporated into the equivalent site in IgA2. Insertion of the IgA1 half hinge into IgA2 did not affect antigen binding capacity or the functional activity of the hybrid molecule, as judged by its ability to bind to IgA Fcα receptors and trigger respiratory bursts in neutrophils. Although the IgA2/A1 hybrid contained only half of the IgA1 hinge, it was found to be cleaved by a variety of different bacterial IgA1 proteases, including representatives of those that cleave IgA1 in the different duplicated halves of the hinge, namely, those ofPrevotella melaninogenica,Streptococcus pneumoniae,S. sanguis,Neisseria meningitidistypes 1 and 2,N. gonorrhoeaetypes 1 and 2, andHaemophilus influenzaetype 2. Thus, for these enzymes the recognition site for IgA1 cleavage is contained within half of the IgA1 hinge region; additional distal elements, if required, are provided by either an IgA1 or an IgA2 framework. In contrast, the IgA2/A1 hybrid appeared to be resistant to cleavage withS. oralisand someH. influenzaetype 1 IgA1 proteases, suggesting these enzymes require additional determinants for efficient substrate recognition.
Priming of a β-Galactosidase (β-GAL)-Specific Type 1 Response in BALB/c Mice Infected with β-GAL-TransfectedLeishmania major
Authors: Chakkalath Hrishekesh R. , Siddiqui Afzal A. , Shankar Anuraj H. , Dobson Deborah E. , Beverley Stephen M. , Titus Richard G. 
Published: July 2002

ABSTRACTTo determine whether an ongoing response toLeishmania majorwould affect the response to a non-cross-reacting, non-leishmanial antigen, susceptible BALB/c mice and resistant C3H mice were infected withL. majorparasites expressingEscherichia coliβ-galactosidase (β-GAL); this parasite was designatedL. major-βGAL. BALB/c and C3H mice responded to infection withL. major-βGALby mounting a CD4 T-cell response to both parasite antigens and to the reporter antigen, β-GAL. The phenotypes of these T cells were characterized after generating T-cell lines from infected mice. As expected, BALB/c mice responded to infection withL. major-βGALby producing interleukin 4 in response to the parasite and C3H mice produced gamma interferon (IFN-γ) in response to the parasite and β-GAL. Interestingly, however, BALB/c mice produced IFN-γ in response to β-GAL. Taken together, these results demonstrate that priming of IFN-γ-producing cells can occur in BALB/c mice despite the fact the animals are simultaneously mounting a potent Th2 response toL. major.
Stability of
Borrelia burgdorferi bdr
Loci In Vitro and In Vivo
Authors: Zückert Wolfram R. , Barbour Alan G. 
Published: July 2002

ABSTRACT

The Lyme disease spirochete
Borrelia burgdorferi
expresses diverse subsurface yet antigenically cross-reactive Bdr protein paralogs from distinct circular- and linear-plasmid loci. We assessed the possible effects of in vitro and in vivo growth on
bdr
locus structure, searching for recombinational events leading to either deletions or insertions of central repeat units or novel amino- and carboxy-terminus combinations. Our data indicate that, apart from plasmid loss during in vitro cultivation, the
bdr
paralog loci of strain B31 are stable. This suggests that recombinatorial variation of
bdr
genes is not essential for persistent mammalian infection.
Chronic Atrophic Gastritis in SCID Mice Experimentally Infected withCampylobacter fetus
Authors: Young Vincent B. , Dangler Charles A. , Fox James G. , Schauer David B. 
Published: July 2002

ABSTRACTCampylobacter fetusis a cause of enteritis and invasive extraintestinal disease in humans. In order to develop an animal model ofC. fetusinfection, outbred ICR SCID mice were orally challenged with a clinical isolate ofC. fetus. The stomachs of SCID mice were heavily colonized withC. fetus, and colonization was associated with the development of chronic atrophic gastritis. This lesion was characterized by an inflammatory infiltrate of granulocytes and macrophages that over time resulted in a loss of specialized parietal and chief cells in the corpus and the appearance of a metaplastic mucous epithelium. This lesion bears similarity to that encountered during experimental murine infection withHelicobacter pyloriorHelicobacter felis. Despite colonization of the cecum and colon tissues byC. fetusin SCID mice, no lesions were noted in these tissues. A follow-up study confirmed these findings for SCID mice and also demonstrated thatC. fetuscould also infect the gastric mucosa of wild-type, outbred ICR mice. However, in ICR mice, the anatomic extent of colonization was more limited and the severity of inflammation and epithelial alterations was significantly less than that observed in infected SCID mice. The stomach may represent an unrecognized environmental niche forCampylobacterspecies.
Localization of
Haemophilus ducreyi
at the Pustular Stage of Disease in the Human Model of Infection
Authors: Bauer Margaret E. , Spinola Stanley M. 
Published: July 2002

ABSTRACT

To localize
Haemophilus ducreyi
in vivo, human subjects were experimentally infected with
H. ducreyi
until they developed a painful pustule or for 14 days. Lesions were biopsied, and biopsy samples were fixed in 4% paraformaldehyde, and cryosectioned. Sections were stained with polyclonal anti-
H. ducreyi
antiserum or
H. ducreyi
-specific monoclonal antibodies (MAbs) and fluorescently tagged secondary antibodies and examined by confocal microscopy. We identified
H. ducreyi
in 16 of 18 pustules but did not detect bacteria in the one papule examined.
H. ducreyi
was observed as individual cells and in clumps or chains. Staining with MAbs 2D8, 5C9, 3B9, 2C7, and 9D12 demonstrated that
H. ducreyi
expresses the major pilus subunit, FtpA, the 28-kDa outer membrane protein Hlp, the 18-kDa outer membrane protein PAL, and the major outer membrane protein (MOMP) or OmpA2 in vivo. By dual staining with polyclonal anti-
H. ducreyi
antiserum and MAbs that recognize human skin components, we observed bacteria within the neutrophilic infiltrates of all positively staining pustules and in the dermis of 10 of 16 pustules. We were unable to detect bacteria associated with keratinocytes in the samples examined. The data suggest that
H. ducreyi
is found primarily in association with neutrophils and in the dermis at the pustular stage of disease in the human model of infection.
Effect of Preexisting Immunity to
Salmonella
on the Immune Response to Recombinant
Salmonella enterica
Serovar Typhimurium Expressing a
Porphyromonas gingivalis
Hemagglutinin
Authors: Kohler James J. , Pathangey Latha B. , Gillespie Sheila R. , Brown Thomas A. 
Published: July 2002

ABSTRACT

Recombinant
Salmonella
strains expressing foreign heterologous genes have been extensively studied as live oral vaccine delivery vectors. We have investigated the mucosal and systemic immune responses following oral immunization with a recombinant
Salmonella enterica
serovar Typhimurium expressing the hemagglutinin HagB from
Porphyromonas gingivalis
, a suspected etiological agent of adult periodontal disease. We have previously shown a primary mucosal and systemic response following oral immunization with χ4072/pDMD1 and recall responses following boosting at 14 weeks after primary immunization. In this study, we examined the effects of earlier boosting as well as the effects of deliberately induced immunity to the
Salmonella
carrier strain on subsequent immune responses. Mice boosted at week 7 following immunization, a point which corresponded to the peak of the primary response, generally showed lower responses than those boosted at week 14. When mice were preimmunized with the
Salmonella
carrier alone and then immunized with the recombinant strain 7 or 14 weeks later, significant reductions were seen for serum immunoglobulin G (IgG) antibodies at week 14 and for salivary IgA at week 7. No reductions were seen in serum IgA or vaginal wash IgA antibodies. Mice appear to be refractory to boosting with orally administered salmonellae at 7 weeks. Deliberate immunization with the carrier strain did not appreciably affect recall responses at 14 weeks, with the exception of the serum IgG responses, nor did it affect colonization of the Peyer's patches.
Possible Release of an ArgGlyArgProGln Pentapeptide with Innate Immunity Properties from Acidic Proline-Rich Proteins by Proteolytic Activity in Commensal
Streptococcus
and
Actinomyces
Species
Authors: Li Tong , Bratt Per , Jonsson Andreas P. , Ryberg Mats , Johansson Ingegerd , Griffiths William J. , Bergman Tomas , Strömberg Nicklas 
Published: July 2002

ABSTRACT

This study suggests degradation of salivary acidic proline-rich proteins (PRPs) into potential innate-immunity-like peptides by oral
Streptococcus
and
Actinomyces
species. PRP degradation paralleled cleavage of Pro-containing substrates. PRP degradation by
S. gordonii
strain SK12 instantly released a Pyr
1
-Pro
104
Pro
105
and a Gly
111
-Pro
149
Gln
150
peptide together with a presumed Arg
106
Gly
107
Arg
108
Pro
109
Gln
110
pentapeptide. The synthetic Arg
106
Gly
107
Arg
108
Pro
109
Gln
110
peptide desorbed bound bacteria and counteracted sucrose-induced decrease of dental plaque pH in vitro.
Human Resistance toPlasmodium falciparumIncreases during Puberty and Is Predicted by Dehydroepiandrosterone Sulfate Levels
Authors: Kurtis Jonathan D. , Mtalib Ramadhan , Onyango Frederick K. , Duffy Patrick E. 
Published: July 2002

ABSTRACTImmunity toPlasmodium falciparumdevelops slowly in areas of endemicity, and this is often ascribed to poorly immunogenic or highly variant parasite antigens. However, among populations newly exposed to malaria, adults acquire immunity more rapidly than children. We examined the relationship between pubertal development and resistance toP. falciparum. During two transmission seasons in western Kenya, we treated the same cohort of young males to eradicateP. falciparumand then obtained blood smears each week for 4 months. We determined pubertal development by Tanner staging and by levels of dehydroepiandrosterone sulfate (DHEAS) and testosterone in plasma. In multivariate and age-stratified analyses, we examined the effect of pubertal development on resistance to malaria. In both seasons (n= 248 and 144 volunteers, respectively), older males were less susceptible than younger males. Age-related decreases in the frequency and density of parasitemia were greatest during puberty (15- to 20-year-olds). DHEAS and testosterone were significant independent predictors of resistance toP. falciparumparasitemia, even after accounting for the effect of age. Fifteen- to 20-year-old males with high DHEAS levels had a 72% lower mean parasite density (P< 0.01) than individuals with low DHEAS levels. Similarly, 21- to 35-year-old males with high DHEAS levels had a 92% lower mean parasite density (P< 0.001) and 48% lower frequency of parasitemia (P< 0.05) than individuals with low DHEAS levels. These data suggest that the long period needed to attain full immunity could be explained as a consequence of host development rather than as the requirement to recognize variant or poorly immunogenic parasite antigens.
Cloning and Expression of theActinobacillus actinomycetemcomitansThioredoxin (trx) Gene and Assessment of Cytokine Inhibitory Activity
Authors: Henderson Brian , Tabona Peter , Poole Stephen , Nair Sean P. 
Published: July 2002

ABSTRACTThioredoxin is a ubiquitous redox control and cell stress protein. Unexpectedly, in recent years, thioredoxins have been found to exhibit both cytokine and chemokine activities, and there is increasing evidence that this class of protein plays a role in the pathogenesis of inflammatory diseases. In spite of this evidence, it has been reported that the oral bacterium and periodontopathogenActinobacillus actinomycetemcomitanssecretes an immunosuppressive factor (termed suppressive factor 1 [SF1] [T. Kurita-Ochiai and K. Ochiai, Infect. Immun. 64:50–54, 1996]) whose N-terminal sequence, we have determined, identifies it as thioredoxin. We have cloned and expressed the gene encoding the thioredoxin ofA. actinomycetemcomitansand have purified the protein to homogeneity. TheA. actinomycetemcomitans trxgene has 52 and 76% identities, respectively, to thetrxgenes ofEscherichia coliandHaemophilus influenzae. Enzymatic analysis revealed that the recombinant protein had the expected redox activity. When the recombinant thioredoxin was tested for its capacity to inhibit the production of cytokines by human peripheral blood mononuclear cells, it showed no significant inhibitory capacity. We therefore conclude that the thioredoxin ofA. actinomycetemcomitansdoes not act as an immunosuppressive factor, at least with human leukocytes in cultures, and that the identity of SF1 remains to be elucidated.
Enterotoxigenic
Escherichia coli
TibA Glycoprotein Adheres to Human Intestine Epithelial Cells
Authors: Lindenthal Christoph , Elsinghorst Eric A. 
Published: July 2002

ABSTRACT

Enterotoxigenic
Escherichia coli
(ETEC) is capable of invading epithelial cell lines derived from the human ileum and colon. Two separate invasion loci (
tia
and
tib
) that direct noninvasive
E. coli
strains to adhere to and invade cultured human intestine epithelial cells have previously been isolated from the classical ETEC strain
H10407
. The
tib
locus directs the synthesis of TibA, a 104-kDa outer membrane glycoprotein. Synthesis of TibA is directly correlated with the adherence and invasion phenotypes of the
tib
locus, suggesting that this protein is an adhesin and invasin. Here we report the purification of TibA and characterization of its biological activity. TibA was purified by continuous-elution preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Purified TibA was biotin labeled and then shown to bind to HCT8 human ileocecal epithelial cells in a specific and saturable manner. Unlabeled TibA competed with biotin-labeled TibA, suggesting the presence of a specific TibA receptor in HCT8 cells. These results show that TibA acts as an adhesin. Polyclonal anti-TibA antiserum inhibited invasion of ETEC strain
H10407
and of recombinant
E. coli
bearing
tib
locus clones, suggesting that TibA also acts as an invasin. The ability of TibA to direct epithelial cell adhesion suggests a role for this protein in ETEC pathogenesis.
Regulated Antigen Expression in Live RecombinantSalmonella entericaSerovar Typhimurium Strongly Affects Colonization Capabilities and Specific CD4+-T-Cell Responses
Authors: Bumann Dirk 
Published: July 2002

ABSTRACTRegulated antigen expression can influence the immunogenicity of live recombinantSalmonellavaccines, but a rational optimization has remained difficult since important aspects of this effect are incompletely understood. Here, attenuatedSalmonella entericaserovar Typhimurium SL3261 strains expressing the model antigen GFP_OVA were used to quantify in vivo antigen levels by flow cytometry and to simultaneously follow the crucial early steps of antigen-specific T-cell responses in mice that are transgenic for a T-cell receptor recognizing ovalbumin. Among seven tested promoters,PpagChas the highest activity in murine tissues combined with low in vitro expression, whereasPtachas a comparable in vivo and a very high in vitro activity. Both SL3261 (pPpagCGFP_OVA) and SL3261 (pPtacGFP_OVA) cells can induce potent ovalbumin-specific cellular immune responses following oral administration, but doses almost 1,000-fold lower are sufficient for the in vivo-inducible construct SL3261 (pPpagCGFP_OVA) compared to SL3261 (pPtacGFP_OVA). This efficacy difference is largely explained by impaired early colonization capabilities of SL3261 (pPtacGFP_OVA) cells. Based on the findings of this study, appropriate in vivo expression levels for any given antigen can be rationally selected from the increasing set of promoters with defined properties. This will allow the improvement of recombinantSalmonellavaccines against a wide range of pathogens.
Arginine-143 of
Yersinia enterocolitica
YopP Crucially Determines Isotype-Related NF-κB Suppression and Apoptosis Induction in Macrophages
Authors: Ruckdeschel Klaus , Richter Kathleen , Mannel Oliver , Heesemann Jürgen 
Published: July 2002

ABSTRACT

Pathogenic
Yersinia
spp. counteract host defense mechanisms by modulating the cellular signal relay in response to infection. Subversion of the antiapoptotic NF-κB signaling pathway by the
Yersinia enterocolitica
virulence protein YopP crucially determines the induction of apoptosis in
Yersinia
-infected macrophages. Here, we analyzed a panel of pathogenic, phylogenetically distinct
Y. enterocolitica
serotypes for their abilities to trigger macrophage apoptosis.
Y. enterocolitica
from the highly pathogenic serogroup O8 was substantially more effective in apoptosis induction than
Yersinia
from the serogroups O3 and O9. Complementation of
yopP
-knockout mutants revealed that this effect was specifically conferred by the serogroup O8 YopP. The amino acid sequences of YopPO8 and YopPO9 share 94% identity, and both YopP isotypes were found to interact with the NF-κB-activating kinase IKKβ in macrophages. However, selectively, YopPO8 mediated efficient inhibition of IKKβ activities, which led to substantial suppression of NF-κB activation. To localize the YopPO8-related effector domain, we interchanged stretches of amino acids and single amino acid residues between YopPO8 and YopPO9. Functional characterization of the resulting mutants revealed a major role of the arginine-143 residue in determining the inhibitory impact of YopP on IKKβ activity and survival of macrophages.
Allelic Variation within
Helicobacter pylori babA
and
babB
Authors: Pride David T. , Meinersmann Richard J. , Blaser Martin J. 
Published: July 2002

ABSTRACT

Helicobacter pylori
strains show both geographic and disease-associated allelic variation. We investigated the diversity present in two genes,
babA
and
babB
, which are members of a paralogous family of outer membrane proteins. Eleven family members within a single
H. pylori
strain, predicted to encode proteins with substantial N- and C-terminal similarity to each other, were classified as
babA
paralogues. In their central regions, most are less than 54% related to one another. Examining the
babA
and
babB
central regions in 42
H. pylori
strains from different geographic locales, we identified five different allele groups of
babA
(AD1 to AD5) and three different allele groups of
babB
(BD1 to BD3). Phylogenetic analysis revealed that the allelic groupings of
babA
and
babB
are independent of one another and that, for both, geographic variation is present. Analysis of synonymous and nonsynonymous substitutions in these regions showed that
babA
is more diverse, implying an earlier origin than that of the same region of
babB
, but that the
babA
diversity region may have more functional constraints. Although recombination has been central to the evolution of both genes, with
babA
and
babB
showing low mean compatibility scores and homoplasy ratios of 0.71 and 0.67, respectively, recombination is not sufficient to obscure evidence of clonal descent. Despite the involvement of
babA
in binding to the host blood group antigen Lewis B, neither the presence of different
babA
allele groups nor that of different
babB
allele groups is a determining factor in Lewis B binding of
H. pylori
strains.
Safety and Immunogenicity of ImprovedShigellaO-Specific Polysaccharide-Protein Conjugate Vaccines in Adults in Israel
Authors: Passwell Justen H. , Harlev Efrat , Ashkenazi Shai , Chu Chiayung , Miron Dan , Ramon Reut , Farzan Naheed , Shiloach Joseph , Bryla Dolores A. , Majadly Fathy , Roberson Robin , Robbins John B. , Schneerson Rachel 
Published: July 2002

ABSTRACTData suggest that the O-specific polysaccharide (O-SP) domain of the lipopolysaccharide (LPS) ofShigellaspecies is both an essential virulence factor and a protective antigen and that a critical level of serum immunoglobulin G (IgG) to this antigen will confer immunity to shigellosis. Because covalent attachment of polysaccharides to proteins increases their immunogenicity, especially in infants and in young children, the O-SP ofShigellaspecies were bound to medically useful proteins, and the safety and immunogenicity of the resultant conjugates were confirmed in adults and 4- to 7-year-old children. Succinylation of the carrier protein improved the immunogenicity ofShigellaconjugates in mice and increased their yield. Based on these results, a clinical trial of O-SP conjugates ofShigella sonneiandShigella flexneri2a bound to succinylated mutantPseudomonas aeruginosaexotoxin A (rEPAsucc) or native or succinylatedCorynebacterium diphtheriaetoxin mutant (CRM9 or CRM9succ) was conducted in healthy adults. The conjugates were safe and immunogenic.S. sonnei-CRM9,S. sonnei-CRM9succ, andS. sonnei-rEPAsuccelicited significant rises of geometric mean (GM) IgG anti-LPS within 1 week of injection (P< 0.001). At 26 weeks, the GM anti-LPS levels elicited by these three conjugates were similar and higher than their prevaccination levels (P< 0.0001). GM IgG anti-LPS levels elicited byS. flexneri2a-rEPAsuccwere significantly higher than those elicited byS. flexneri2a-rCRM9succat all intervals after injection. At 26 weeks, the levels of IgG anti-LPS in vaccinees were higher than their prevaccination levels (P< 0.0001). The serum antibody responses were specific, as there was no significant rise of anti-LPS to the heterologous O-SP in any vaccinee. Both conjugates elicited statistically significant rises of serum antibodies to the injected carrier protein. At 6 months, these fiveShigellaconjugates elicited higher fold rises than similar conjugates (D. N. Taylor et al., Infect. Immun. 61:3678–3687, 1993). Based on these data, we choseS. sonnei-CRM9 andS. flexneri2a-rEPAsuccfor evaluation in children.