bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mycobacterial Dose Defines the Th1/Th2 Nature of the Immune Response Independently of Whether Immunization Is Administered by the Intravenous, Subcutaneous, or Intradermal Route
Authors: Power Carl A. , Wei Guojian , Bretscher Peter A. 
Published: December 2019

ABSTRACTIt is believed that cell-mediated immunity alone can containMycobacterium tuberculosis, the pathogen responsible for tuberculosis. The induction of antibody, or of a mixed cell-mediated/humoral response, is associated with tuberculous disease. It is therefore important to determine the conditions of immunization with bacille Calmette Guérin (BCG), the attenuated strain ofMycobacterium bovisused to vaccinate humans against tuberculosis, that optimally induces an exclusive cell-mediated, Th1 response. Such a determination will then allow an assessment of whether the generation of such an exclusive Th1 response results in the generation of a Th1 imprint against mycobacteria. This Th1 imprint would ensure that the Th1 response is predominant following any challenge. We therefore tested the proposition that the dose of mycobacteria used for immunization generally determines the Th1/Th2 nature of the ensuing response. Our results demonstrate that relatively low doses lead to an almost exclusive cell-mediated, Th1 response, while higher doses induce a mixed Th1/Th2 response. Furthermore, the dependence on dose is independent of whether BCG is administered intravenously, subcutaneously, or intradermally. The implications of our findings to understanding how different classes of immunity are induced, to the epidemiology of tuberculosis, and to the design of effective vaccination strategies are discussed.
Expression of Plasminogen Activator Pla of
Yersinia pestis
Enhances Bacterial Attachment to the Mammalian Extracellular Matrix
Authors: Lähteenmäki Kaarina , Virkola Ritva , Sarén Anne , Emödy Levente , Korhonen Timo K. 
Published: December 2019

ABSTRACT

The effect of the plasminogen activator Pla of
Yersinia pestis
on the adhesiveness of bacteria to the mammalian extracellular matrix was determined.
Y. pestis
KIM D27 harbors the 9.5-kb plasmid pPCP1, encoding Pla and pesticin; the strain efficiently adhered to the reconstituted basement membrane preparation Matrigel, to the extracellular matrix prepared from human lung NCI-H292 epithelial cells, as well as to immobilized laminin. The isogenic strain
Y. pestis
KIM D34 lacking pPCP1 exhibited lower adhesiveness to both matrix preparations and to laminin. Both strains showed weak adherence to type I, IV, and V collagens as well as to human plasma and cellular fibronectin. The Pla-expressing recombinant
Escherichia coli
LE392(pC4006) exhibited specific adhesiveness to both extracellular matrix preparations as well as to laminin. The Pla-expressing strains showed a low-affinity adherence to another basement membrane component, heparan sulfate proteoglycan, but not to chondroitin sulfate proteoglycan. The degradation of radiolabeled laminin, heparan sulfate proteoglycan, or human lung extracellular matrix by the Pla-expressing recombinant
E. coli
required the presence of plasminogen, and degradation was inhibited by the plasmin inhibitors aprotinin and α2-antiplasmin. Our results indicate a function of Pla in enhancing bacterial adhesion to extracellular matrices.
Y. pestis
also exhibits a low level of Pla-independent adhesiveness to extracellular matrices.
Relationship between Hydroxy Fatty Acids and Prostaglandin E2in Gingival Tissue
Authors: Nichols Frank , Maraj Baliram 
Published: December 2019

ABSTRACTBacterial hydroxy fatty acids and alpha-hydroxy fatty acids have been demonstrated in complex lipid extracts of subgingival plaque and gingival tissue. However, little is known about the relationship between these hydroxy fatty acids in plaque and gingival tissues or the significance of these complex lipids in promoting inflammatory periodontal disease. The present study determined the percentages of ester-linked and amide-linked hydroxy fatty acids in complex lipids recovered from plaque and gingival tissue samples and the relationship between bacterial hydroxy fatty acids and alpha-hydroxy fatty acids in the lipid extracts. To evaluate a potential role for these hydroxy fatty acids in inflammatory periodontal disease, gingival tissue samples were examined for a relationship between prostaglandin E2(PGE2) and hydroxy fatty acids recovered in gingival lipid. This investigation demonstrated that alpha-hydroxy fatty acids are only ester linked in plaque lipids but are largely amide linked in gingival tissue lipids. Furthermore, the level of alpha-hydroxy fatty acid in gingival lipid is directly related to the level of the bacterial hydroxy fatty acid 3-OHiso-branched C17:0(3-OH iC17:0) in the same lipid extract. However, the relationship between hydroxy fatty acids in gingival lipids does not parallel the fatty acid relationship observed in plaque lipids. Finally, alpha-hydroxy fatty acid levels in gingival tissue lipids correlate directly with the recovery of PGE2in the same tissue samples. These results demonstrate that alpha-hydroxy fatty acid levels in gingival lipids are directly related to both 3-OH iC17:0bacterial lipid levels and PGE2levels. These results indicate that in periodontal tissues there are unusual host-parasite interactions involving penetration of bacterial lipid in association with an altered gingival lipid metabolism and prostaglandin synthesis.
Estimation of Group B Streptococcus Type III Polysaccharide-Specific Antibody Concentrations in Human Sera Is Antigen Dependent
Authors: Bhushan Reva , Anthony Bascom F. , Frasch Carl E. 
Published: December 2019

ABSTRACTThe presence of immunoglobulin G (IgG) antibodies against group B streptococcus (GBS) type III polysaccharide (PS) has been correlated with protection against GBS disease. The GBS type III PS is structurally similar to the pneumococcal type 14 PS, differing only in the presence of sialic acid residues. Four different preparations of GBS type III PS were evaluated for their specificity in enzyme-linked immunosorbent assay (ELISA): free PS, free PS mixed with methylated human serum albumin (mHSA), PS conjugated to biotin and PS conjugated to human serum albumin. Three groups of human sera were used to evaluate these PS preparations: sera from recipients of a GBS PS vaccine, sera from women receiving a GBS type III PS-tetanus toxoid conjugate vaccine, and sera from nonimmunized healthy women of childbearing age. Estimated antibody concentrations were different depending on the PS preparation used. Using any of the four preparations, we were able to measure ≤0.05 μg of IgG antibody to the GBS type III PS per ml. The specificity of the assay was determined by competitive inhibition with homologous and heterologous PS. The pneumococcal type 14 PS did not inhibit binding of antibody to the native GBS type III PS in sera from adults receiving the GBS PS vaccine or in sera from nonimmunized adults (except serum G9). The pneumococcal type 14 PS inhibited 50% in sera from recipients of GBS type III conjugate vaccine and in serum G9 when GBS type III PS conjugated to biotin or to HSA was used as antigen in ELISA. These data show that free GBS type III PS or PS mixed with mHSA is a sensitive and specific antigen for ELISA and that conjugation can alter the antigenic specificity of a PS.
Specific-Antibody-Secreting Cells in the Rectums and Genital Tracts of Nonhuman Primates following Vaccination
Authors: Eriksson Kristina , Quiding-Järbrink Marianne , Osek Jacek , Möller Åke , Björk Stellan , Holmgren Jan , Czerkinsky Cecil 
Published: December 2019

ABSTRACTTo determine optimal strategies to induce specific-antibody-secreting cells (specific ASC) in the rectal and vaginal mucosae, we immunized monkeys with a prototype mucosal immunogen, cholera toxin (CT), given locally or via gastric or parenteral administration. Repeated rectal or vaginal CT immunizations induced strong mucosal and systemic ASC responses. The mucosal responses were, however, confined to the immunization sites and comprised high levels of both specific antitoxin immunoglobulin A (IgA) and IgG. Large numbers of specific IgA and IgG ASC were detected in cell suspensions from dissociated genital and rectal tissues, demonstrating local accumulation of effector B cells at these sites. Intragastric immunization with CT did not per se give rise to cervicovaginal or rectal ASC responses but did prime for a rectal IgA ASC response to local booster immunization. Both rectal and vaginal immunizations also induced circulating blood IgG ASC and IgA ASC. In conclusion, these results show that local administration of antigen to the rectal or vaginal mucosa results in higher ASC responses than systemic or distant mucosal delivery. Furthermore, both the vaginal and the rectal mucosae can serve as inductive sites for systemic ASC responses. These observations should be relevant to the development of vaccines against sexually transmitted diseases such as that caused by human immunodeficiency virus.
Streptococcus sanguis-Induced Platelet Clotting in Rabbits and Hemodynamic and Cardiopulmonary Consequences
Authors: Meyer Maurice W. , Gong Ke , Herzberg Mark C. 
Published: December 2019

ABSTRACTBy mimicking hemostatic structural domains of collagen,Streptococcus sanguis(aggregation-positive phenotype; Agg+) induces platelets to aggregate in vitro. To test the hypothesis that aggregation occurs in vivo,S. sanguis(Agg+or Agg−suspension) was infused intravenously into rabbits. The extent of hemodynamic and cardiopulmonary changes and the fate of circulating platelets were Agg+strain dose dependent. Within 45 to 50 s of the start of infusion, 40 × 108CFU of the Agg+strain caused increased blood pressure. Thirty seconds after infusion, other changes occurred. Intermittent electrocardiographic abnormalities (13 of 15 rabbits), ST-segment depression (10 of 15 rabbits), and preventricular contractions (7 of 15 rabbits) manifested at 3 to 7 min, with frequencies dose dependent. Respiratory rate and cardiac contractility increased during this phase. Blood catecholamine concentration, thrombocytopenia, accumulation of111Indium-labeled platelets in the lungs, and ventricular axis deviation also showed dose dependency. Rabbits were unaffected by inoculation of an Agg−strain. Therefore, Agg+S. sanguisinduced platelet aggregation in vitro. Platelet clots caused hemodynamic changes, acute pulmonary hypertension, and cardiac abnormalities, including ischemia.
Characterization of Human Immunoglobulin (Ig) Isotype and IgG Subclass Response to
Bartonella henselae
Infection
Authors: McGill Svena L. , Regnery Russell L. , Karem Kevin L. 
Published: December 2019

ABSTRACT

Serologic parameters of cat scratch disease (CSD) were evaluated by Western blot analysis. Sera from patients with serologically confirmed CSD antigen were screened for immunoglobulin (Ig) isotype-specific as well as IgG subclass-specific reactivity against
Bartonella henselae
whole-cell antigen.
Bartonella
-negative control sera were used to determine baseline antibody activity. Heterogeneous
B. henselae
-specific IgG reactivity with numerous protein bands, ranging from >150 to <17 kDa, was observed. Though individual banding patterns were variable, one approximately 83-kDa
B. henselae
protein (Bh83) was immunoreactive with all CSD sera tested, suggesting it is a conserved antigen during infection. Bh83 was not recognized by reference human antisera against
Rickettsia rickettsii
,
Chlamydia
group positive,
Treponema pallidum
,
Orientia tsutsugamushi
,
Fransciscella tularensis
,
Ehrlichia chaffeensis
,
Mycoplasma pneumoniae
, and
Escherichia coli
, although other cross-reactive proteins were evident. Significantly, CSD sera failed to recognize the 83-kDa protein when tested against
Bartonella quintana
antigen, though sera from
B. quintana
-infected patients did react to Bh83. This cross-reactivity suggests epitope conservation during infection with
B. henselae
or
B. quintana
. Western blot analysis further revealed similar banding patterns when
B. henselae
was reacted against the Ig isotypes IgG and IgG
1
and both secretory and alpha chains of IgA. Neither IgM nor IgE reacted significantly to
Bartonella
antigen by our Western blot analysis. Dissection of the antibody response at the IgG subclass level indicated that prominent antigen recognition was limited to IgG
1
. These observations provide insight into induced immunity during CSD and provide evidence for conserved epitope expression during infection with
B. henselae
or
B. quintana
.
Filamentous Hemagglutinin ofBordetella bronchisepticaIs Required for Efficient Establishment of Tracheal Colonization
Authors: Cotter Peggy A. , Yuk Ming H. , Mattoo Seema , Akerley Brian J. , Boschwitz Jeff , Relman David A. , Miller Jeff F. 
Published: December 2019

ABSTRACTAdherence to ciliated respiratory epithelial cells is considered a critical early step inBordetellapathogenesis. ForBordetella pertussis, the etiologic agent of whooping cough, several factors have been shown to mediate adherence to cells and cell lines in vitro. These putative adhesins include filamentous hemagglutinin (FHA), fimbriae, pertactin, and pertussis toxin. Determining the precise roles of each of these factors in vivo, however, has been difficult, due in part to the lack of natural-host animal models for use withB. pertussis. Using the closely related speciesBordetella bronchiseptica, and by constructing both deletion mutation and ectopic expression mutants, we have shown that FHA is both necessary and sufficient for mediating adherence to a rat lung epithelial (L2) cell line. Using a rat model of respiratory infection, we have shown that FHA is absolutely required, but not sufficient, for tracheal colonization in healthy, unanesthetized animals. FHA was not required for initial tracheal colonization in anesthetized animals, however, suggesting that its role in establishment may be dedicated to overcoming the clearance action of the mucociliary escalator.
The (α2→8)-Linked Polysialic Acid Capsule and Lipooligosaccharide Structure Both Contribute to the Ability of Serogroup BNeisseria meningitidisTo Resist the Bactericidal Activity of Normal Human Serum
Authors: Kahler C. M. , Martin L. E. , Shih G. C. , Rahman M. M. , Carlson R. W. , Stephens D. S. 
Published: December 2019

ABSTRACTThe molecular basis for the resistance of serogroup BNeisseria meningitidisto the bactericidal activity of normal human sera (NHS) was examined with a NHS-resistant, invasive serogroup B meningococcal isolate and genetically and structurally defined capsule-, lipooligosaccharide (LOS)-, and sialylation-altered mutants of the wild-type strain. Expression of the (α2→8)-linked polysialic acid serogroup B capsule was essential for meningococcal resistance to NHS. The very NHS-sensitive phenotype of acapsular mutants (99.9 to 100% killed in 10, 25, and 50% NHS) was not rescued by complete LOS sialylation or changes in LOS structure. However, expression of the capsule was necessary but not sufficient for a fully NHS-resistant phenotype. In an encapsulated background, loss of LOS sialylation by interrupting the α2,3 sialyltransferase gene,lst, increased sensitivity to 50% NHS. In contrast, replacement of the lacto-N-neotetraose α-chain (Galβ1-4GlcNAcβ1-3Galβ1-4Glc) with glucose extensions (GlcN) in agalEmutant resulted in a strain resistant to killing by 50% NHS at all time points. Encapsulated meningococci expressing a Hep2(GlcNAc)→KDO2→lipid A LOS without an α-chain demonstrated enhanced sensitivity to 50% NHS (98% killed at 30 min) mediated through the antibody-dependent classical complement pathway. Encapsulated LOS mutants expressing truncated Hep2→KDO2→lipid A and KDO2→lipid A structures were also sensitive to 50% NHS (98 to 100% killed at 30 min) but, unlike the wild-type strain and mutants with larger oligosaccharide structures, they were killed by hypogammaglobulinemic sera. These data indicate that encapsulation is essential but that the LOS structure contributes to the ability of serogroup BN. meningitidisto resist the bactericidal activity of NHS.
Filarial Nematode Parasites Secrete a Homologue of the Human Cytokine Macrophage Migration Inhibitory Factor
Authors: Pastrana Diana V. , Raghavan Nithyakalyani , FitzGerald Peter , Eisinger Stephen W. , Metz Christine , Bucala Richard , Schleimer Robert P. , Bickel Carol , Scott Alan L. 
Published: December 2019

ABSTRACTFilarial nematode parasites establish long-term chronic infections in the context of an antiparasite immunity that is strongly biased toward a Th2 response. The mechanisms that lead to this Th2 bias toward filarial antigens are not clear, but one possibility is that the parasites produce molecules that have the capacity to proactively modify their immunological environment. Here we report that filarial parasites of humans secrete a homologue of the human proinflammatory cytokine macrophage migration inhibitory factor (MIF) that has the capability of modifying the activity of human monocytes/macrophages. A cDNA clone isolated from aBrugia malayiinfective-stage larva expression library encoded a 12.5-kDa protein product (Bm-MIF) with 42% identity to human and murine MIF. MIF homologues were also found to be expressed in the related filarial speciesWuchereria bancroftiandOnchocerca volvulus.Bm-mifwas transcribed by adult and larval parasites, and the protein product was found in somatic extracts and in the parasite’s excretory-secretory products. Immunohistocytochemistry revealed thatBm-MIF was localized to cells of the hypodermis/lateral chord, the uterine wall, and larvae developing in utero. Unexpectedly, the activities of recombinantBm-MIF and human MIF on human monocytes/macrophages were found to be similar. When placed with monocytes/macrophages in a cell migration assay,Bm-MIF inhibited random migration. When placed away from cells,Bm-MIF induced an increase in monocyte/macrophage migration that was specifically inhibited by neutralizing anti-Bm-MIF antibodies.Bm-MIF is the first demonstration that helminth parasites produce cytokine homologues that have the potential to modify host immune responses to promote parasite survival.
Local Cytokine Response inHelicobacter pylori-Infected Subjects
Authors: Lindholm C. , Quiding-Järbrink M. , Lönroth H. , Hamlet A. , Svennerholm A.-M. 
Published: December 2019

ABSTRACTThe host immune response toHelicobacter pyloriinfection might be of importance with regard to the outcome of infection by this organism, e.g., to explain why only a proportion of infected subjects develop peptic ulcers. In this study we have analyzed the local response of different cytokines—i.e., the proinflammatory interleukin-1β, (IL-1β), IL-6, tumor necrosis factor alpha, and IL-8; the immunoregulatory gamma interferon (IFN-γ); and IL-4; and the anti-inflammatory transforming growth factor beta (TGF-β)—in antral biopsy specimens fromH. pylori-infected duodenal ulcer (DU) patients and asymptomatic (AS) carriers (i.e., with chronic gastritis only). For comparison, biopsy specimens from uninfected healthy individuals were also analyzed. An immunohistochemical technique was used to allow quantification of the cytokine responses as well as identification of the cell types associated with the cytokine expression. We found that the levels of all of the studied cytokines except IL-4 were increased in theH. pylori-infected subjects compared to the levels in the healthy individuals. Our results indicate that the antral cytokine response is of the Th1type since IFN-γ, but not IL-4, was up-regulated both inH. pylori-infected DU patients and in AS carriers. However, there were no significant differences in either proinflammatory or immunoregulatory cytokine levels whenH. pylori-infected subjects with and without peptic ulcers were compared. Some of the cytokines, particularly IL-1β and TGF-β, were also found in the gastric mucosae of healthy, uninfected subjects. We also showed that the gastric epithelium contributes substantially to the antral cytokine response of the proinflammatory cytokines IL-1β and IL-6 in addition to IL-8.
Identification of a
Chlamydia trachomatis
Serovar E Urogenital Isolate Which Lacks the Cryptic Plasmid
Authors: Stothard Diane R. , Williams James A. , Van Der Pol Barbara , Jones Robert B. 
Published: December 2019

ABSTRACT

Our laboratory recently recovered
Chlamydia trachomatis
in tissue culture from a urogenital specimen which tested negative by commercial plasmid-based PCR. Immunotyping and
omp1
sequencing identified the isolate as a serovar E isolate. Further investigation by PCR and Southern hybridization indicated that this isolate lacks the chlamydial cryptic plasmid.
Sialic Acid-Dependent Recognition of Laminin by
Penicillium marneffei
Conidia
Authors: Hamilton A. J. , Jeavons L. , Youngchim S. , Vanittanakom N. , Hay R. J. 
Published: December 2019

ABSTRACT

Immunofluorescence microscopy demonstrated that laminin bound to the surface of
Penicillium marneffei
conidia. Attachment of
P. marneffei
conidia in an adherence assay was inhibited by soluble laminin and anti-laminin antibody.
N
-Acetylneuraminic acid abolished adherence, indicating an interaction mediated by a sialic acid-specific lectin.
Phagocytic and Tumor Necrosis Factor Alpha Response of Human Mast Cells following Exposure to Gram-Negative and Gram-Positive Bacteria
Authors: Arock Michel , Ross Elaine , Lai-Kuen René , Averlant Geneviève , Gao Zhimin , Abraham Soman N. 
Published: December 2019

ABSTRACTRecent studies have implicated rodent mast cells in the innate immune response to infectious bacteria. We report that cord blood-derived human mast cells (CBHMC) obtained from culture of cord blood progenitors phagocytozed and killed various gram-negative and gram-positive bacteria and simultaneously released considerable amounts of tumor necrosis factor alpha. Overall, the extent of the endocytic and exocytic response of CBHMC correlated with the number of adherent bacteria. Thus, human mast cells are intrinsically capable of mediating microbial recognition and of actively contributing to the host defense against bacteria.
Immunogenicity of a 48-Kilodalton Recombinant T-Cell-Reactive Protein of
Coccidioides immitis
Authors: Kirkland Theo N. , Thomas Pei Wang , Finley Fred , Cole Garry T. 
Published: December 2019

ABSTRACT

The outcome of coccidioidomycosis depends to a large extent on the effectiveness of the T-cell-mediated immune (CMI) response to the fungal pathogen. For this reason, identification of
Coccidioides immitis
antigens which stimulate T cells is important for understanding the nature of host defense against the organism and essential for the development of an effective vaccine. Here we describe the immunogenicity of a 48-kDa T-cell-reactive protein (TCRP). The antigen is expressed by parasitic cells and localized in the cytoplasm. It stimulates the proliferative response and production of gamma interferon by T cells of mice immunized with
C. immitis
spherules. Specific antibody reactive with the recombinant TCRP (rTCRP) was detected in sera of patients with confirmed coccidioidal infection, and the highest titers of antibody to the recombinant protein correlated with elevated titers to the serodiagnostic complement fixation antigen of
C. immitis
. These results suggest that the TCRP is presented to the host during the course of infection. Immunization of BALB/c and C3H/HeN mice with the rTCRP affords a modest but significant level of protection against an intraperitoneal challenge with
C. immitis
. It is suggested that the rTCRP may be able to contribute to a multicomponent vaccine designed to stimulate CMI response against the parasitic cycle of
C. immitis.