bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clearance ofCitrobacter rodentiumRequires B Cells but Not Secretory Immunoglobulin A (IgA) or IgM Antibodies
Authors: Maaser Christian , Housley Michael P. , Iimura Mitsutoshi , Smith Jennifer R. , Vallance Bruce A. , Finlay B. Brett , Schreiber John R. , Varki Nissi M. , Kagnoff Martin F. , Eckmann Lars 
Published: May 2004

ABSTRACTCitrobacter rodentium, a murine model pathogen for human enteropathogenicEscherichia coli, predominantly colonizes the lumen and mucosal surface of the colon and cecum and causes crypt hyperplasia and mucosal inflammation. Mice infected withC. rodentiumdevelop a secretory immunoglobulin A (IgA) response, but the role of B cells or secretory antibodies in host defense is unknown. To address this question, we conducted oralC. rodentiuminfections in mice lacking B cells, IgA, secreted IgM, polymeric Ig receptor (pIgR), or J chain. Normal mice showed peak bacterial numbers in colon and feces at 1 week and bacterial eradication after 3 to 4 weeks. B-cell-deficient mice were equally susceptible initially but could not control infection subsequently. Tissue responses showed marked differences, as infection of normal mice was accompanied by transient crypt hyperplasia and mucosal inflammation in the colon and cecum at 2 but not 6 weeks, whereas B-cell-deficient mice had few mucosal changes at 2 weeks but severe epithelial hyperplasia with ulcerations and mucosal inflammation at 6 weeks. The functions of B cells were not mediated by secretory antibodies, since mice lacking IgA or secreted IgM or proteins required for their transport into the lumen, pIgR or J chain, clearedC. rodentiumnormally. Nonetheless, systemic administration of immune sera reduced bacterial numbers significantly in normal and pIgR-deficient mice, and depletion of IgG abrogated this effect. These results indicate that host defense againstC. rodentiumdepends on B cells and IgG antibodies but does not require production or transepithelial transport of IgA or secreted IgM.
Age-Specific Immunoglobulin G (IgG) and IgA to Pneumococcal Protein Antigens in a Population in Coastal Kenya
Authors: Laine Catherine , Mwangi Tabitha , Thompson Claudette M. , Obiero Jacktone , Lipsitch Marc , Scott J. Anthony G. 
Published: May 2004

ABSTRACT

Streptococcus pneumoniae
is the primary etiological agent of community-acquired pneumonia and a major cause of meningitis and bacteremia. Three conserved pneumococcal proteins—pneumolysin, pneumococcal surface adhesin A (PsaA), and pneumococcal surface protein A (PspA)—are currently being investigated as vaccine candidates. Such protein-based vaccines, if proven effective, could provide a cheaper alternative to conjugate vaccine formulae. Few data from sub-Saharan Africa exist concerning the development of natural antibody to these antigens, however. To investigate the age-specific development of antiprotein immunoglobulin G (IgG) and IgA antibody responses, the sera of 220 persons 2 weeks to 84 years of age from coastal Kenya were assayed using enzyme-linked immunosorbent assays. IgG and IgA antibody responses to each antigen were observed in all age groups. Serum concentrations of IgG and IgA antibody responses to PspA and PdB (a recombinant toxoid derivative of pneumolysin), but not to PsaA, increased significantly with age (
P
< 0.001). No decline was observed in the sera of the elderly. Anti-protein IgG concentrations were only weakly correlated (0.30 <
r
< 0.56;
P
< 0.0001), as were IgA concentrations (0.24 <
r
< 0.54;
P
< 0.0001).
RecombinantMycobacterium bovisBCG Expressing the Sm14 Antigen ofSchistosoma mansoniProtects Mice from Cercarial Challenge
Authors: Varaldo Paula B. , Leite Luciana C. C. , Dias Waldely O. , Miyaji Eliane N. , Torres Fabio I. G. , Gebara Vera C. , Armôa Geraldo R. G. , Campos Adriano S. , Matos Denise C. S. , Winter Nathalie , Gicquel Brigitte , Vilar Mônica M. , McFadden Johnjoe , Almeida Marilia S. , Tendler Miriam , McIntosh Douglas 
Published: May 2004

ABSTRACTThe Sm14 antigen ofSchistosoma mansoniwas cloned and expressed inMycobacterium bovisBCG as a fusion with theMycobacterium fortuitumβ-lactamase protein under the control of its promoter, pBlaF*; the protein was localized in the bacterial cell wall. The rBCG-Sm14 strain was shown to be relatively stable in cultured murine and bovine monocytes in terms of infectivity, bacterial persistence, and plasmid stability. The immunization of mice with rBCG-Sm14 showed no induction of anti-Sm14 antibodies; however, splenocytes of immunized mice released increased levels of gamma interferon upon stimulation with recombinant Sm14 (rSm14), indicating an induction of a Th1-predominant cellular response against Sm14. Mice immunized with one or two doses of rBCG-Sm14 and challenged with liveS. mansonicercaria showed a 48% reduction in worm burden, which was comparable to that obtained by immunization with three doses of rSm14 purified fromEscherichia coli. The data presented here further enhance the status of Sm14 as a promising candidate antigen for the control of schistosomiasis and indicate that a one-dose regimen of rBCG-Sm14 could be considered a convenient means to overcome many of the practical problems associated with the successful implementation of a multiple-dose vaccine schedule in developing countries.
Complement Activation and Complement-Dependent Inflammation byNeisseria meningitidisAre Independent of Lipopolysaccharide
Authors: Sprong Tom , Møller Anne-Sophie W. , Bjerre Anna , Wedege Elisabeth , Kierulf Peter , van der Meer Jos W. M. , Brandtzaeg Petter , van Deuren Marcel , Mollnes T. E. 
Published: May 2004

ABSTRACTFulminant meningococcal sepsis has been termed the prototypical lipopolysaccharide (LPS)-mediated gram-negative septic shock. Systemic inflammation by activated complement and cytokines is important in the pathogenesis of this disease. We investigated the involvement of meningococcal LPS in complement activation, complement-dependent inflammatory effects, and cytokine or chemokine production. Whole blood anticoagulated with lepirudin was stimulated with wild-typeNeisseria meningitidisH44/76 (LPS+), LPS-deficientN. meningitidisH44/76lpxA(LPS−), or purified meningococcal LPS (NmLPS) at concentrations that were relevant to meningococcal sepsis. Complement activation products, chemokines, and cytokines were measured by enzyme-linked immunosorbent assays, and granulocyte CR3 (CD11b/CD18) upregulation and oxidative burst were measured by flow cytometry. The LPS+and LPS−N. meningitidisstrains both activated complement effectively and to comparable extents. Purified NmLPS, used at a concentration matched to the amount present in whole bacteria, did not induce any complement activation. Both CR3 upregulation and oxidative burst were also induced, independent of LPS. Interleukin-1β (IL-1β), tumor necrosis factor alpha, and macrophage inflammatory protein 1α production was predominantly dependent on LPS, in contrast to IL-8 production, which was also markedly induced by the LPS−meningococci. In this whole blood model of meningococcal sepsis, complement activation and the immediate complement-dependent inflammatory effects of CR3 upregulation and oxidative burst occurred independent of LPS.
Suppression of Serum Antibody Responses by Pertussis Toxin after Respiratory Tract Colonization byBordetella pertussisand Identification of an Immunodominant Lipoprotein
Authors: Carbonetti Nicholas H. , Artamonova Galina V. , Andreasen Charlotte , Dudley Edward , Mays R. Michael , Worthington Zoe E. V. 
Published: May 2004

ABSTRACTPertussis toxin (PT), a virulence factor secreted byBordetella pertussis, contributes to respiratory tract infection and disease caused by this pathogen. By comparing a wild-type (WT)B. pertussisstrain to a mutant strain with an in-frame deletion of theptxgenes encoding PT (ΔPT), we recently found that the lack of PT confers a significant defect in respiratory tract colonization in mice after intranasal inoculation. In this study, we analyzed serum antibody responses in mice infected with the WT or ΔPT strain and found that infection with the ΔPT strain elicited greater responses to severalB. pertussisantigens than did infection with the WT, despite the lower colonization level achieved by the ΔPT strain. The same enhanced antibody response was observed after infection with a strain expressing an enzymatically inactive PT; but this response was not observed after infection withB. pertussismutant strains lacking filamentous hemagglutinin or adenylate cyclase toxin, nor when purified PT was administered with the ΔPT inoculum, indicating a specific role for PT activity in this immunosuppressive effect. In particular, there were consistent strong serum antibody responses to one or more low-molecular-weight antigens after infection with the ΔPT strain. These antigens were Bvg independent, membrane localized, and also expressed by the closely related pathogensBordetella parapertussisandBordetella bronchiseptica. Two-dimensional gel electrophoresis and mass spectrometry were used to identify one of the immunodominant low-molecular-weight antigens as a protein with significant sequence homology to peptidoglycan-associated lipoprotein in several other gram-negative bacterial species. However, a serum antibody response to this protein alone did not protect mice against respiratory tract infection byB. pertussis.
Cryptococcus neoformans
Capsule Structure Evolution In Vitro and during Murine Infection
Authors: Garcia-Hermoso Dea , Dromer Françoise , Janbon Guilhem 
Published: May 2004

ABSTRACT

Cryptococcus neoformans
capsule structure modifications after prolonged in vitro growth or in vivo passaging have been reported previously. However, nothing is known about the dynamics of these modifications or about their environmental specificities. In this study, capsule structure modifications after mouse passaging and prolonged in vitro culturing were analyzed by flow cytometry using the glucuronoxylomannan-specific monoclonal antibody E1. The capsule structures of strains recovered after 0, 1, 8, and 35 days were compared by using the level of E1-specific epitope expression and its cell-to-cell heterogeneity within a given cell population. In vitro, according to these parameters, the diversity of the strains was higher on day 35 than it was initially, suggesting the absence of selection during in vitro culturing. In contrast, the diversity of the strains recovered from the brain tended to decrease over time, suggesting that selection of more adapted strains had occurred. The strains recovered on day 35 from the spleen and the lungs had different phenotypes than the strains isolated from the brain of the same mouse on the same day, thus strongly suggesting that there is organ specificity for
C. neoformans
strain selection. Fingerprinting of the strains recovered in vitro and in vivo over time confirmed that genotypes evolved very differently in vitro and in vivo, depending on the environment. Overall, our results suggest that organ-specific selection can occur during cryptococcosis.
Clostridium sordelliiLethal Toxin Is Maintained in a Multimeric Protein Complex
Authors: Voth Daniel E. , Qa'Dan Maen , Hamm Elaine E. , Pelfrey Joy M. , Ballard Jimmy D. 
Published: May 2004

ABSTRACTClostridium sordelliilethal toxin (TcsL) is distinct among large clostridial toxins (LCTs), as it is markedly reduced in its rate of intoxication at pH 8.0 yet is cytotoxic at pH 4.0. Results from the present study suggest that TcsL's slow rate of intoxication at pH 8.0 is linked to formation of a high-molecular-weight complex containing dissociable pH 4.0-sensitive polypeptides. The cytosolic delivery of TcsL's enzymatic domain by using a surrogate cell entry system resulted in cytopathic effect rates similar to those of other LCTs at pH 8.0, further indicating that rate-limiting steps occurred at the point of cell entry. Since these rate-limiting steps could be overcome at pH 4.0, TcsL was examined across a range of pH values and was found to dissociate into distinct 45- to 55-kDa polypeptides between pH 4.0 and pH 5.0. The polypeptides reassociated when shifted back to pH 8.0. At pH 8.0, this complex was resistant to sodium dodecyl sulfate (SDS) and multiple proteases; however, following dissociation, the polypeptides became protease sensitive. Dissociation of TcsL, and cytotoxicity, could be blocked by preincubation with ethylene glycol bis(sulfosuccinimidylsuccinate), resulting in cross-linking of the polypeptides. TcsL was also examined at pH 8.0 by using SDS-agarose gel electrophoresis and transmission electron microscopy and was found to exist in a higher-molecular-weight complex which resolved at a size exceeding 750 kDa and also dissociated at pH 4.0. However, this complex did not reassemble following a shift back to pH 8.0. Collectively, these data suggest that TcsL is maintained in a protease-resistant, high-molecular-weight complex, which dissociates at pH 4.0, leading to cytotoxicity.
Fungal Metabolite Gliotoxin Inhibits Assembly of the Human Respiratory Burst NADPH Oxidase
Authors: Tsunawaki Shohko , Yoshida Lucia S. , Nishida Satoshi , Kobayashi Toshihiro , Shimoyama Takashi 
Published: May 2004

ABSTRACTReactive oxygen species are a critical weapon in the killing ofAspergillus fumigatusby polymorphonuclear leukocytes (PMN), as demonstrated by severe aspergillosis in chronic granulomatous disease. In the present study,A. fumigatus-produced mycotoxins (fumagillin, gliotoxin [GT], and helvolic acid) are examined for their effects on the NADPH oxidase activity in human PMN. Of these mycotoxins, only GT significantly and stoichiometrically inhibits phorbol myristate acetate (PMA)-stimulated O2−generation, while the other two toxins are ineffective. The inhibition is dependent on the disulfide bridge of GT, which interferes with oxidase activation but not catalysis of the activated oxidase. Specifically, GT inhibits PMA-stimulated events: p47phoxphosphorylation, its incorporation into the cytoskeleton, and the membrane translocation of p67phox, p47phox, and p40phox, which are crucial steps in the assembly of the active NADPH oxidase. Thus, damage to p47phoxphosphorylation is likely a key to inhibiting NADPH oxidase activation. GT does not inhibit the membrane translocation of Rac2. The inhibition of p47phoxphosphorylation is due to the defective membrane translocation of protein kinase C (PKC) βII rather than an effect of GT on PKC βII activity, suggesting a failure of PKC βII to associate with the substrate, p47phox, on the membrane. These results suggest thatA. fumigatusmay confront PMN by inhibiting the assembly of the NADPH oxidase with its hyphal product, GT.
Mitogenicity of the Recombinant Mycobacterial 27-Kilodalton Lipoprotein Is Not Connected to Its Antiprotective Effect
Authors: Hovav Avi-Hai , Davidovitch Liuba , Nussbaum Gabriel , Mullerad Jacob , Fishman Yolanta , Bercovier Herve 
Published: May 2004

ABSTRACTWe reported previously that even though immunization with the recombinant mycobacterial 27-kDa lipoprotein (r27) induced a Th1-type response in mice, the vaccinated mice became more susceptible to challenge withMycobacterium tuberculosis. In this study we show that r27 stimulates naive splenocytes to proliferate. Acylation of r27 was crucial for this effect, since a nonacylated mutant of r27, termed r27ΔSP, failed to stimulate splenocytes either in vitro or in vivo. Depletion experiments indicated that only B cells were proliferating in a T-cell-independent manner. We also found that r27 is recognized by TLR2, which is involved in mitogenic stimulation. Interestingly, r27 but not r27ΔSP induced high gamma interferon levels in splenocyte supernatants, whereas no significant interleukin-2 levels were detected. Since B-cell polyclonal activation might aggravate pathogen infection, we asked whether the antiprotective effect of the r27 lipoprotein is associated with its mitogenicity. We showed that, as in the case of r27, immunization of mice with the nonmitogenic r27ΔSP lipoprotein resulted in increasedM. tuberculosismultiplication. We conclude that the antiprotective effect of the r27 lipoprotein must be linked to properties of the polypeptide portion of the lipoprotein rather than to its lipid moiety and its mitogenicity.
Association of Type 2 Cytokines with Hepatic Fibrosis in HumanSchistosoma mansoniInfection
Authors: Ribeiro de Jesus Amélia , Magalhães Andréa , Gonzalez Miranda Delfin , Gonzalez Miranda Roberval , Araújo Maria Ilma , Almeida de Jesus Adriana , Silva Angela , Santana Luciana B. , Pearce Edward , Carvalho Edgar M. 
Published: May 2004

ABSTRACTThe objective of this study was to evaluate the role of cytokines in hepatic fibrosis in the prehepatosplenic and early hepatosplenic stages of schistosomiasis mansoni. Hepatic fibrosis was classified by ultrasonography of 94 patients. Immunological evaluation was performed by the measurement of secreted cytokines (interleukin-5 [IL-5], IL-10, IL-13, gamma interferon, tumor necrosis factor alpha, and transforming growth factor β) in peripheral blood mononuclear cells (PBMC) stimulated bySchistosoma mansoniantigens. Significantly, higher levels of IL-5, IL-10, and IL-13 were found in supernatants of soluble egg antigen-stimulated PBMC from subjects with degree III hepatic fibrosis compared to patients with degree I or II fibrosis. Significant increases in IL-5 and IL-13 levels were also observed in some of the subjects who remained untreated for 1 year following initial assessment and developed more serious fibrosis during this period. The data suggest a role for type 2 cytokines in hepatic fibrosis in human schistosomiasis mansoni.
Characterization of theicmHandicmFGenes Required forLegionella pneumophilaIntracellular Growth, Genes That Are Present in Many Bacteria Associated with Eukaryotic Cells
Authors: Zusman Tal , Feldman Michal , Halperin Einat , Segal Gil 
Published: May 2004

ABSTRACTLegionella pneumophila, the causative agent of Legionnaires' disease, replicates intracellularly within a specialized phagosome of mammalian and protozoan host cells, and the Icm/Dot type IV secretion system has been shown to be essential for this process. Unlike all the other known Icm/Dot proteins, the IcmF protein, which was described before, and the IcmH protein, which is characterized here, have homologous proteins in many bacteria (such asYersinia pestis,Salmonella enterica,Rhizobium leguminosarum, andVibrio cholerae), all of which associate with eukaryotic cells. Here, we have characterized theL. pneumophila icmHandicmFgenes and found that both genes are present in 16 differentLegionellaspecies examined. TheicmHandicmFgenes were found to be absolutely required for intracellular multiplication inAcanthamoeba castellaniiand partially required for intracellular growth in HL-60-derived human macrophages, for immediate cytotoxicity, and for salt sensitivity. Mutagenesis of the predicted ATP/GTP binding site of IcmF revealed that the site is partially required for intracellular growth inA. castellanii. Analysis of the regulatory region of theicmHandicmFgenes, which were found to be cotranscribed, revealed that it contains at least two regulatory elements. In addition, anicmH::lacZfusion was shown to be activated during stationary phase in a LetA- and RelA-dependent manner. Our results indicate that although theicmHandicmFgenes probably have a different evolutionary origin than the rest of theicm/dotgenes, they are part of theicm/dotsystem and are required forL. pneumophilapathogenesis.
A Cardiac Myosin-Specific Autoimmune Response Is Induced by Immunization withTrypanosoma cruziProteins
Authors: Leon Juan S. , Daniels Melvin D. , Toriello Krista M. , Wang Kegiang , Engman David M. 
Published: May 2004

ABSTRACTTrypanosoma cruziis the protozoan parasite that causes Chagas' heart disease, a potentially fatal cardiomyopathy prevalent in Central and South America. Infection withT. cruziinduces cardiac myosin autoimmunity in susceptible humans and mice, and this autoimmunity has been suggested to contribute to cardiac inflammation. To address howT. cruziinduces cardiac myosin autoimmunity, we investigated whether immunity toT. cruziantigens could induce cardiac myosin-specific autoimmunity in the absence of live parasites. We immunized A/J mice with aT. cruziBrazil-derived protein extract emulsified in complete Freund's adjuvant and found that these mice developed cardiac myosin-specific delayed-type hypersensitivity (DTH) and autoantibodies in the absence of detectable cardiac damage. The induction of autoimmunity was specific since immunization with extracts of the related protozoan parasiteLeishmania amazonensisdid not induce myosin autoimmunity. The immunogenetic makeup of the host was important for this response, since C57BL/6 mice did not develop cardiac myosin DTH upon immunization withT. cruziextract. Perhaps more interesting, mice immunized with cardiac myosin developedT. cruzi-specific DTH and antibodies. This DTH was also antigen specific, since immunization with skeletal myosin and myoglobin did not induceT. cruzi-specific immunity. These results suggest that immunization with cardiac myosin orT. cruziantigen can induce specific, bidirectionally cross-reactive immune responses in the absence of detectable cardiac damage.
A Novel Lectin, DltA, Is Required for Expression of a Full Serum Resistance Phenotype inHaemophilus ducreyi
Authors: Leduc Isabelle , Richards Patricia , Davis Crystal , Schilling Birgit , Elkins Christopher 
Published: May 2004

ABSTRACTHaemophilus ducreyi, the causative agent of chancroid, is highly resistant to the complement-mediated bactericidal activity of normal human serum (NHS). Previously, we identified DsrA (for ducreyi serum resistance A), a major factor required for expression of the serum resistance phenotype inH. ducreyi. We describe here a second outer membrane protein, DltA (for ducreyi lectin A), which also contributes to serum resistance inH. ducreyi. IsogenicdltAmutants, constructed in 35000HP wild-type and FX517dsrAbackgrounds, were more susceptible to the bactericidal effects of NHS than each respective parent, demonstrating the additive effect of the mutations. Furthermore, expression ofdltAinH. influenzaestrain Rd rendered this highly susceptible strain partially resistant to 5% NHS compared to a vector-control strain. Although primary basic local alignment search tool analysis of thedltAopen reading frame revealed no close bacterial homologue, similarity to the β-chain of the eukaryotic lectin ricin was noted. DltA shares highly conserved structural motifs with the ricin β chain, such as cysteines and lectin-binding domains. To determine whetherdltAwas a lectin, ligand blots and affinity chromatography experiments were performed. DltA was affinity purified on immobilized lactose andN-acetylgalactosamine, and N-glycosylated but not glycosidase-treated model glycoproteins bound DltA. These data indicate that DltA is a lectin with specificity for lactose-related carbohydrates (CHO) and is important forH. ducreyiserum resistance.