bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of Antibody Isotype Responses toSchistosoma mansoniin an Immunologically Naive Immigrant Population: Influence of Infection Duration, Infection Intensity, and Host Age
Authors: Naus Cynthia W. A. , Kimani Gachuhi , Ouma John H. , Fulford Anthony J. C. , Webster Michelle , van Dam Govert J. , Deelder André M. , Butterworth Anthony E. , Dunne David W. 
Published: December 2019

ABSTRACTWe have identified the influence of host and parasite factors that give rise to characteristic antibody isotype profiles with age seen in human populations living in different areas of schistosomiasis endemicity. This is important in the immunobiology of this disease. It is also of interest in the context of human responses to chronic antigen stimulation, vaccines, allergens, and other pathogens. In populations exposed to endemic schistosomiasis, factors such as intensity and duration of infection are age dependent. They therefore confound the influence of host age on antiparasite responses. Here, we resolved these confounding factors by comparing the developing antibody responses of an immunologically naive immigrant population as they acquired the infection for the first time with those of chronically infected resident inhabitants of the same region ofSchistosoma mansoniendemicity in Kenya. Recent arrival in the area strongly favored immunoglobulin G3 (IgG3) responses against the parasite. The antibody isotype responses associated with human susceptibility to reinfection after chemotherapy were elevated in those suffering high intensities of infection (IgG4 responses against worm and egg antigens) or were characteristic responses of young children irrespective of the intensity or duration of infection (IgG2 responses against egg antigen). IgE responses against the adult worm, a response associated with resistance to reinfection after chemotherapy, increased with the ages of infected individuals and were also favored in those currently suffering higher intensities of infection.
Wheat Germ Agglutinin Induces NADPH-Oxidase Activity in Human Neutrophils by Interaction with Mobilizable Receptors
Authors: Karlsson Anna 
Published: December 2019

ABSTRACTWheat germ agglutinin (WGA), a lectin with specificity forN-acetylglucosamine and sialic acid, was investigated with respect to its ability to activate the NADPH-oxidase of in vivo-exudated neutrophils (obtained from a skin chamber), and the activity was compared to that of peripheral blood neutrophils. The exudate cells responded to WGA, by both releasing reactive oxygen species into the extracellular milieu and producing oxygen metabolites intracellularly. The peripheral blood cells were unresponsive. To mimic the in vivo-exuded neutrophils with regards to receptor exposure, peripheral blood neutrophils were induced to mobilize their granules and vesicles to varying degrees (in vitro priming), prior to challenge with WGA. The oxidative response to WGA increased with increasing levels of granule mobilization, and the receptor(s) could be shown to reside in the secretory vesicles and/or the gelatinase granules in resting neutrophils. Several WGA-binding glycoproteins were detected in subcellular fractions containing these organelles. The extra- and intracellular NADPH-oxidase responses showed differences in sialic acid dependency, indicating that these two responses are mediated by different receptor structures.
Effect of Peroxisome Proliferator-Activated Receptor Alpha Activators on Tumor Necrosis Factor Expression in Mice during Endotoxemia
Authors: Hill Molly R. , Clarke Stephen , Rodgers Kerry , Thornhill Brandi , Peters Jeffrey M. , Gonzalez Frank J. , Gimble Jeffrey M. 
Published: December 2019

ABSTRACTInflammatory mediators orchestrate the host immune and metabolic response to acute bacterial infections and mediate the events leading to septic shock. Tumor necrosis factor (TNF) has long been identified as one of the proximal mediators of endotoxin action. Recent studies have implicated peroxisome proliferator-activated receptor alpha (PPARα) as a potential target to modulate regulation of the immune response. Since PPARα activators, which are hypolipidemic drugs, are being prescribed for a significant population of older patients, it is important to determine the impact of these drugs on the host response to acute inflammation. Therefore, we examined the role of PPARα activators on the regulation of TNF expression in a mouse model of endotoxemia. CD-1 mice treated with dietary fenofibrate or Wy-14,643 had fivefold-higher lipopolysaccharide (LPS)-induced TNF plasma levels than LPS-treated control-fed animals. Higher LPS-induced TNF levels in drug-fed animals were reflected physiologically in significantly lower glucose levels in plasma and a significantly lower 50% lethal dose than those in LPS-treated control-fed animals. Utilizing PPARα wild-type (WT) and knockout (KO) mice, we showed that the effect of fenofibrate on LPS-induced TNF expression was indeed mediated by PPARα. PPARα WT mice fed fenofibrate also had a fivefold increase in LPS-induced TNF levels in plasma compared to control-fed animals. However, LPS-induced TNF levels were significantly decreased and glucose levels in plasma were significantly increased in PPARα KO mice fed fenofibrate compared to those in control-fed animals. Data from peritoneal macrophage studies indicate that Wy-14,643 modestly decreased TNF expression in vitro. Similarly, overexpression of PPARα in 293T cells decreased activity of a human TNF promoter-luciferase construct. The results from these studies suggest that any anti-inflammatory activity of PPARα in vivo can be masked by other systemic effects of PPARα activators.
Mouse β-Defensin 3 Is an Inducible Antimicrobial Peptide Expressed in the Epithelia of Multiple Organs
Authors: Bals Robert , Wang Xiaorong , Meegalla Rupalie L. , Wattler Sigrid , Weiner Daniel J. , Nehls Michael C. , Wilson James M. 
Published: December 2019

ABSTRACT

One component of host defense at mucosal surfaces is epithelium-derived peptides with antimicrobial activity called defensins. We describe in this report the isolation and characterization of a murine homologue of human β-defensin 2 (hBD-2) called mouse β-defensin 3 (mBD-3). The predicted amino acid sequence shows the hallmark features of other known epithelial defensins, including the ordered array of six cysteine residues. Analysis of a genomic clone of mBD-3 revealed two exons separated by a 1.7-kb intron. The mBD-3 gene is localized at the proximal portion of chromosome 8, the site where genes for mouse α- and β-defensins are found. Under basal condition, mBD-3 transcripts were detected at low levels in epithelial cells of surface organs, such as the intestine and lung. After instillation of
Pseudomonas aeruginosa
PAO1 into mouse airways, mBD-3-specific mRNA was upregulated significantly not only in large airways but also in the small bowel and liver. Recombinant mBD-3 peptide, produced from a baculovirus expression system, showed antimicrobial activity against
P. aeruginosa
PAO1 (MIC of 8 μg/ml) and
Escherichia coli
D31 (MIC of 16 μg/ml) in a salt-dependent manner. This study demonstrates that a murine homologue of hBD-2 is present in the respiratory system and other mucosal surfaces. These similarities between murine and human host defense apparatus provide further impetus to evaluate the mouse as a model for studying the human innate host defense system.
Fatal Granuloma Necrosis without Exacerbated Mycobacterial Growth in Tumor Necrosis Factor Receptor p55 Gene-Deficient Mice Intravenously Infected withMycobacterium avium
Authors: Ehlers Stefan , Benini Jochen , Kutsch Stefanie , Endres Robert , Rietschel Ernst T. , Pfeffer Klaus 
Published: December 2019

ABSTRACTThe pathogenesis of mycobacterial infections is associated with the formation of granulomas in which both antibacterial protection and tissue damage take place concomitantly. We used murineMycobacterium aviuminfection to compare the development of granulomatous lesions in intravenously infected tumor necrosis factor receptor p55 (TNFRp55) gene-deficient (p55−/−) mice to the development of granulomatous lesions inM. avium-infected syngeneic C57BL/6 (p55+/+) mice. Up to 5 weeks after infection with either the highly virulentM. aviumstrain TMC724 or the intermediately virulentM. aviumstrain SE01, bacterial counts in the liver, spleen, and lung of p55−/−mice were identical to or lower than those in infected p55+/+mice. However, the formation of mononuclear cell foci in the liver was delayed by approximately 2 to 3 weeks in p55−/−mice compared to the results obtained for infected p55+/+mice. Despite comparable bacterial loads, granulomas in p55−/−mice underwent progressive necrosis, causing damage to the surrounding liver tissue. The appearance of necrotizing granulomas was associated with the death of all infected p55−/−mice, regardless of the virulence of theM. aviumstrain used for infection. Granulomatous lesions in the liver contained three times as many CD3+cells in p55−/−mice yet appeared more diffuse than in p55+/+mice. Semiquantitative reverse transcription-PCR studies revealed that prior to mouse death, interleukin-12 (IL-12) and gamma interferon mRNA levels were up regulated in the livers of infected p55−/−mice, while mRNA levels for tumor necrosis factor, the inducible isoform of nitric-oxide synthase (iNOS), and IL-10 were similar to those found in infected p55+/+mice. In response to persistent mycobacterial infection, the absence of TNFRp55 causes the disregulation of T-cell–macrophage interactions and results in fatal granuloma necrosis even when adequate antibacterial functions are maintained.
Invasive Lesions Containing Filamentous Forms Produced by a
Candida albicans
Mutant That Is Defective in Filamentous Growth in Culture
Authors: Riggle Perry J. , Andrutis Karl A. , Chen Xi , Tzipori Saul R. , Kumamoto Carol A. 
Published: December 2019

ABSTRACT

A
Candida albicans efg1 cph1
double mutant is nonfilamentous under standard laboratory conditions and avirulent in mice. However, this mutant produced filaments in the tongues of immunosuppressed gnotobiotic piglets and when embedded in agar, demonstrating that an Efg1p- and Cph1p-independent pathway for promotion of filamentous growth exists.
Pneumolysin, a Protein Toxin of
Streptococcus pneumoniae
, Induces Nitric Oxide Production from Macrophages
Authors: Braun Johann S. , Novak Rodger , Gao Geli , Murray Peter J. , Shenep Jerry L. 
Published: December 2019

ABSTRACT

Nitric oxide (NO) production by inducible NO synthase (iNOS) during inflammation is an essential element of antimicrobial immunity but can also contribute to host-induced tissue damage. Under conditions of bacterial sepsis, large amounts of NO are produced, causing hypotension, a critical pathological feature of septic shock. In sepsis caused by gram-positive organisms, the bacterial factors contributing to host NO production are poorly characterized. We show that a soluble toxin of
Streptococcus pneumoniae
, pneumolysin (Pln), is a key component initiating NO production from macrophages. In contrast to wild-type bacteria, a mutant of
S. pneumoniae
lacking Pln failed to elicit NO production from murine macrophages. Purified recombinant Pln induced NO production at low concentrations and independently of exogenous gamma interferon (IFN-γ) priming of RAW 264.7 macrophages. However, IFN-γ was essential for Pln-induced NO production, since primary macrophages from mice lacking the IFN-γ receptor or interferon regulatory factor 1, a transcription factor essential for iNOS expression, failed to produce NO when stimulated with Pln. In addition, Pln acts as an agonist of tumor necrosis factor alpha and interleukin 6 production in macrophages. The properties of Pln, previously identified as a pore-forming hemolysin, also include a role as a general inflammatory agonist.
Cytotoxic T-Cell-Mediated Response againstYersinia pseudotuberculosisin HLA-B27 Transgenic Rat
Authors: Falgarone Géraldine , Blanchard Hervé S. , Riot Bertrand , Simonet Michel , Breban Maxime 
Published: December 2019

ABSTRACTYersinia-induced reactive arthritis is highly associated with HLA-B27, the role of which in defense against the triggering bacteria remains unclear. The aim of this study was to examine the capacity of rats transgenic for HLA-B27 to mount a cytotoxic T-lymphocyte (CTL) response againstY. pseudotuberculosisand to determine the influence of the HLA-B27 transgene on this response. Rats transgenic for HLA-B*2705 and human β2-microglobulin of the 21-4L line, which do not spontaneously develop disease, and nontransgenic syngeneic Lewis (LEW) rats were infected withY. pseudotuberculosis. Lymph node cells were restimulated in vitro, and the presence of forY. pseudotuberculosis-specific CTLs against infected targets was determined. Infection of 21-4L rats triggered a CD8+T cell-mediated cytotoxic response specific forY. pseudotuberculosis. Analysis of this response demonstrated restriction by an endogenous major histocompatibility complex molecule. However, no restriction by HLA-B27 was detected. In addition, kinetics studies revealed a weaker anti-YersiniaCTL response in 21-4L rats than in nontransgenic LEW rats, and the level of cytotoxicity against 21-4L lymphoblast targets sensitized with Y. pseudotuberculosis was lower than that against nontransgenic LEW targets. We conclude that HLA-B27 transgenic rats mount a CTL response againstY. pseudotuberculosisthat is not restricted by HLA-B27. Yet, HLA-B27 exerts a negative effect on the level of this response, which could contribute to impaired defense againstYersinia.
Adhesion of
Tritrichomonas foetus
to Bovine Vaginal Epithelial Cells
Authors: Singh B. N. , Lucas J. J. , Beach D. H. , Shin S. T. , Gilbert R. O. 
Published: December 2019

ABSTRACT

An in vitro culture system of bovine vaginal epithelial cells (BVECs) was developed to study the cytopathogenic effects of
Tritrichomonas foetus
and the role of lipophosphoglycan (LPG)-like cell surface glycoconjugates in adhesion of parasites to host cells. Exposure of BVEC monolayers to
T. foetus
resulted in extensive damage of monolayers. Host cell disruption was measured quantitatively by a trypan blue exclusion assay and by release of
3
H from [
3
H]thymidine-labeled host cells. Results indicated contact-dependent cytotoxicity of host cells by
T. foetus
. The cytopathogenic effect was a function of
T. foetus
density. Metronidazole- or periodate-treated
T. foetus
showed no damage to BVEC monolayers. A related human trichomonad,
Trichomonas vaginalis
, showed no cytotoxic effects, indicating species-specific host-parasite interactions. A direct binding assay was developed and used to investigate the role of a major cell surface LPG-like molecule in host-parasite adhesion. The results of competition experiments showed that the binding to BVECs was displaceable, was saturable, and yielded a typical binding curve, suggesting that specific receptor-ligand interactions mediate the attachment of
T. foetus
to BVECs. Progesterone-treated BVECs showed enhanced parasite binding.
T. foetus
LPG inhibited the binding of
T. foetus
to BVECs; the LPG from
T. vaginalis
and a variety of other glycoconjugates did not. These data imply specificity of LPG on host-parasite adhesion. Periodate-treated parasites showed no adherence to host cells, indicating the involvement of carbohydrate containing molecules in the adhesion process.
Multiple Genes in the Left Half of thecagPathogenicity Island ofHelicobacter pyloriAre Required for Tyrosine Kinase-Dependent Transcription of Interleukin-8 in Gastric Epithelial Cells
Authors: Li Shude D. , Kersulyte Dangeruta , Lindley Ivan J. D. , Neelam Beena , Berg Douglas E. , Crabtree Jean E. 
Published: December 2019

ABSTRACTHelicobacter pyloristrains that contain thecagpathogenicity island (PAI) elicit increased synthesis of gastric C-X-C chemokines, promote neutrophilic infiltration into the gastric epithelium, and stimulate the synthesis of interleukin-8 (IL-8) in cultured gastric epithelial cells. To investigate the effects ofcagPAI genes on the transcription of the IL-8 gene, the Kato-3 gastric epithelial cell line was stably transfected with plasmid DNA containing the IL-8 gene promoter fused to a luciferase reporter gene. The resulting reporter cell line, L5F11, was used to monitor the effects of infection in cell culture byH. pylori26695 and isogenic derivatives with null mutations in genes in thecagPAI on transcription of the IL-8 gene. We found that null mutations in eight open reading frames, including homologs of theAgrobacterium virB9,virB10, andvirB11genes, in the left half of thecagPAI abrogated the induction of IL-8 gene transcription. Further studies with the L5F11 cell line showed that IL-8 gene transcription induced byH. pyloriwas blocked by the protein tyrosine kinase inhibitor herbimycin A but not by the protein kinase C inhibitor calphostin C or by the protein kinase G inhibitor KT5823. IL-8 gene transcription in L5F11 cells could also be induced by the cytokine tumor necrosis factor alpha (TNF-α) without exposure toH. pylori. This TNF-α-induced IL-8 transcription was inhibited by the protein kinase A inhibitor H7, which had no significant effect onH. pylori-induced IL-8 transcription. These studies show that multiple genes in the left half of thecagPAI are essential for the transcription of the IL-8 gene in gastric epithelial cells and that this depends on protein tyrosine kinase activation.
Limited Local and Systemic Antibody Responses toNeisseria gonorrhoeaeduring Uncomplicated Genital Infections
Authors: Hedges Spencer R. , Mayo Matthew S. , Mestecky Jiri , Hook Edward W. , Russell Michael W. 
Published: December 2019

ABSTRACTRepeated infections withNeisseria gonorrhoeaeare common among patients attending sexually transmitted disease clinics. We examined whether previous infections or site of infection altered the local and systemic antigonococcal antibody levels in males and females. Antibodies againstN. gonorrhoeaeMS11 and the patients’ homologous infecting isolates were measured by enzyme-linked immunosorbent assay. In general, the local and systemic immune responses to gonococci were extremely modest. There was a slight increase in serum immunoglobulin G (IgG) against the MS11 strain and the homologous isolates in infected males. Levels of serum IgA1 antibodies against MS11 were slightly higher in infected than in uninfected females. A history of previous infections withN. gonorrhoeaedid not alter the antibody levels in patients with a current infection, suggesting that immunological memory is not induced by uncomplicated gonococcal infections. Antibody responses to infected subjects’ homologous isolates were observed in cervical mucus; IgA1 levels increased while IgG levels decreased. The decline in mucosal IgG against the homologous isolates was less common in subjects having both rectal and cervical infections; otherwise, no effect of rectal involvement was observed. The absence of substantially higher antibody levels to gonococci where there is infection at a site known to contain organized lymphoid tissue suggests that the low levels of responses to uncomplicated infections may not be due simply to an absence of inductive sites in the genital tract. We propose that in addition to its potential ability to avoid the effects of an immune response,N. gonorrhoeaedoes not elicit strong humoral immune responses during uncomplicated genital infections.
Early Acidification of Phagosomes ContainingBrucella suisIs Essential for Intracellular Survival in Murine Macrophages
Authors: Porte Françoise , Liautard Jean-Pierre , Köhler Stephan 
Published: December 2019

ABSTRACTBrucella suisis a facultative intracellular pathogen of mammals, residing in macrophage vacuoles. In this work, we studied the phagosomal environment of these bacteria in order to better understand the mechanisms allowing survival and multiplication ofB. suis. Intraphagosomal pH in murine J774 cells was determined by measuring the fluorescence intensity of opsonized, carboxyfluorescein-rhodamine- and Oregon Green 488-rhodamine-labeled bacteria. Compartments containing liveB. suisacidified to a pH of about 4.0 to 4.5 within 60 min. Acidification ofB. suis-containing phagosomes in the early phase of infection was abolished by treatment of host cells with 100 nM bafilomycin A1, a specific inhibitor of vacuolar proton-ATPases. This neutralization at 1 h postinfection resulted in a 2- to 34-fold reduction of opsonized and nonopsonized viable intracellular bacteria at 4 and 6 h postinfection, respectively. Ammonium chloride and monensin, other pH-neutralizing reagents, led to comparable loss of intracellular viability. Addition of ammonium chloride at 7 h after the beginning of infection, however, did not affect intracellular multiplication ofB. suis, in contrast to treatment at 1 h postinfection, where bacteria were completely eradicated within 48 h. Thus, we conclude that phagosomes withB. suisacidify rapidly after infection, and that this early acidification is essential for replication of the bacteria within the macrophage.
Nine-Year Longitudinal Study of Antibodies to Variant Antigens on the Surface ofPlasmodium falciparum-Infected Erythrocytes
Authors: Giha Haider A. , Staalsoe Trine , Dodoo Daniel , Elhassan Ibrahim M. , Roper Cally , Satti Gwiria M. H. , Arnot David E. , Theander Thor G. , Hviid Lars 
Published: December 2019

ABSTRACTPfEMP1 is an antigenically variable molecule which mediates the adhesion of parasitized erythrocytes to a variety of cell types and which is believed to constitute an important target for naturally acquired protective immune responses in malaria. For 9 years we have monitored individuals living in an area of low-intensity, seasonal, and unstable malaria transmission in eastern Sudan, and we have used this database to study the acquisition, specificity, and duration of the antibody response to variant parasitized erythrocyte surface antigens. Both the levels and the spectrum of reactivity of these antibodies varied considerably among individuals, ranging from low levels of antibodies recognizing only few parasitized erythrocyte surface antigens to high levels of broad-specificity antibodies. In general, episodes of clinical malaria were associated with increases in the levels of parasitized erythrocyte surface-specific antibodies that subsided within months of the attack. This response was often, but not always, specific for the antigenic variants expressed by the parasite isolate causing disease. Our study provides evidence thatPalciparum falciparummalaria is associated with a short-lived, variant-specific antibody response to PfEMP1-like antigens exposed on the surface of parasitized erythrocytes. Furthermore, our data suggest that the antigenic repertoires of variant antigens expressed by different parasite isolates show considerable overlapping, at least under Sahelian conditions of low-intensity, seasonal, and unstable malaria transmission. Finally, we demonstrate the existence of persistent differences among individuals in the capacity to mount antibody responses to variant surface antigens.