bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rhodococcus equi-Specific Cytotoxic T Lymphocytes in Immune Horses and Development in Asymptomatic Foals
Authors: Patton Kristin M. , McGuire Travis C. , Hines Melissa T. , Mealey Robert H. , Hines Stephen A. 
Published: March 2005

ABSTRACTRhodococcus equiis an important cause of pneumonia in young horses; however, adult horses are immune due to their ability to mount protective recall responses. In this study, the hypothesis thatR. equi-specific cytotoxic T lymphocytes (CTL) are present in the lung of immune horses was tested. Bronchoalveolar lavage (BAL)-derived pulmonary T lymphocytes stimulated withR. equilysed infected alveolar macrophages and peripheral blood adherent cells (PBAC). As with CTL obtained from the blood, killing ofR. equi-infected targets by pulmonary effectors was not restricted by equine lymphocyte alloantigen-A (ELA-A; classical major histocompatibility complex class I), suggesting a novel or nonclassical method of antigen presentation. To determine whether or not CTL activity coincided with the age-associated susceptibility to rhodococcal pneumonia, CTL were evaluated in foals.R. equi-stimulated peripheral blood mononuclear cells (PBMC) from 3-week-old foals were unable to lyse either autologous perinatal or mismatched adult PBAC targets. The defect was not with the perinatal targets, as adult CTL effectors efficiently killed infected targets from 3-week-old foals. In contrast, significant CTL activity was present in three of five foals at 6 weeks of age, and significant specific lysis was induced by PBMC from all foals at 8 weeks of age. As with adults, lysis was ELA-A unrestricted. Two previously described monoclonal antibodies, BCD1b3 and CD1F2/1B12.1, were used to examine the expression of CD1, a nonclassical antigen-presenting molecule, on CTL targets. These antibodies cross-reacted with both foal and adult PBAC. However, neither antibody bound alveolar macrophages, suggesting that theR. equi-specific, major histocompatibility complex-unrestricted lysis is not restricted by a surface molecule identified by these antibodies.
Campylobacter jejuni-Induced Cytokine Responses in Avian Cells
Authors: Smith Chris K. , Kaiser Pete , Rothwell Lisa , Humphrey Tom , Barrow Paul A. , Jones Michael A. 
Published: March 2005

ABSTRACTCampylobacter jejuniis a major cause of human inflammatory enteritis. During the course of human disease numerous proinflammatory cytokines are produced. Little is known, however, about the cytokine responses produced during the interaction of this bacterium with the avian host.Campylobacterhas been considered a commensal of the avian host. Any differences in innate responses to this pathogen between the human and avian hosts should lead to a greater understanding of the disease process in humans. We have demonstrated expression of proinflammatory cytokines and chemokines in response toCampylobacterinfection in avian primary chick kidney cells and the avian macrophage cell line HD11. The data indicate thatCampylobactercan stimulate the avian host in a proinflammatory manner. The data strongly suggest that the lack of pathology in vivo is not due to an inability ofCampylobacterto stimulate a proinflammatory response from avian cells.
Interleukin 10- and Fcγ Receptor-Deficient Mice ResolveLeishmania mexicanaLesions
Authors: Buxbaum Laurence U. , Scott Phillip 
Published: March 2005

ABSTRACTInfection of C57BL/6 (B6) mice withLeishmania mexicanais associated with a minimal immune response and chronic disease. Here we show that B6 interleukin 10−/−(IL-10−/−) mice resolve their lesions and exhibit increased gamma interferon (IFN-γ), nitric oxide production, and delayed-type hypersensitivity. This enhanced resistance was dependent upon IL-12p40, since treatment ofL. mexicana-infected IL-10−/−mice with anti-IL-12p40 monoclonal antibody abrogated healing. Antibody-opsonizedL. mexicanainduced IL-10 production by B6 macrophages in vitro, implicating antibody binding to Fc receptors as a mechanism involved in IL-10 production in this infection. Furthermore, B6 FcRγ−/−mice resolveL. mexicanalesions, and lymph node cells from these mice produced less IL-10 and more IFN-γ than cells from infected wild-type mice. These data demonstrate that removal of IL-10 or FcγR leads to resolution ofL. mexicanadisease and support a model in which ligation of FcγR byL. mexicana-bound immunoglobulin G promotes IL-10 production, leading to chronic disease.
Mode of Action of Invasion-Inhibitory Antibodies Directed against Apical Membrane Antigen 1 of
Plasmodium falciparum
Authors: Dutta Sheetij , Haynes J. David , Barbosa Arnoldo , Ware Lisa A. , Snavely Jeffrey D. , Moch J. Kathleen , Thomas Alan W. , Lanar David E. 
Published: March 2005

ABSTRACT

Antibodies against apical membrane antigen 1 (AMA-1) of
Plasmodium falciparum
inhibit merozoite invasion into erythrocytes. Invasion-inhibitory polyclonal AMA-1 antibodies inhibit secondary proteolytic processing and surface redistribution of AMA-1 on merozoites. We present evidence supporting inhibition of processing and redistribution as probable causes of inhibition of invasion by polyclonal antibodies. Polyclonal anti-AMA-1 was much more inhibitory than monoclonal antibody (MAb) 4G2dc1 in an invasion assay. Although both polyclonal and monoclonal immunoglobulin G (IgG) inhibited secondary processing of the 66-kDa form of AMA-1, only polyclonal IgG caused its anomalous processing, inhibited its redistribution, and cross-linked soluble forms of AMA-1 on merozoites. Moreover, Fab fragments of polyclonal IgG that fail to cross-link did not show the enhancement of inhibitory effect over intact IgG, as observed in the case of Fab fragments of MAb 4G2dc1. We propose that although blocking of biologically important sites is a common direct mode of action of anti-AMA-1 antibodies, blocking of AMA-1 secondary processing and redistribution are additional indirect inhibitory mechanisms by which polyclonal IgG inhibits invasion. We also report a processing inhibition assay that uses a C-terminal AMA-1-specific MAb, 28G2dc1, to detect merozoite-bound remnants of processing (∼20 kDa from normal processing to 48 and 44 kDa and ∼10 kDa from anomalous processing to a 52-kDa soluble form of AMA-1). The ratio of intensity of 10-kDa bands to the sum of 10- and 20-kDa bands was positively correlated with inhibition of invasion by polyclonal antibodies. This assay may serve as an important immunochemical correlate for inhibition of invasion.
Epitopes Recognized by a Nonautoreactive Murine Anti-N-Propionyl Meningococcal Group B Polysaccharide Monoclonal Antibody
Authors: Moe Gregory R. , Dave Apurva , Granoff Dan M. 
Published: March 2005

ABSTRACTThe capsular polysaccharide ofNeisseria meningitidisgroup B (MBPS) is a polymer of alpha (2→8)N-acetyl neuraminic acid. The polysaccharide is chemically identical to an autoantigen, polysialic acid (PSA), and is a poor immunogen, even when conjugated to protein carriers. Immunization of mice with MBPS-protein conjugate vaccines, in whichN-acetyl groups have been replaced by propionyl groups (N-Pr MBPS), elicits serum bactericidal antibodies. A subpopulation of these antibodies do not cross-react with human PSA. The reasons for the increased immunogenicity ofN-Pr MBPS and the antigenic targets of the bactericidal nonautoreactive antibodies are unknown. In this study, we investigated the antigenic targets of a protective murine monoclonal antibody (MAb) prepared against aN-Pr MBPS-tetanus toxoid conjugate vaccine. Binding of the MAb toN-Pr MBPS (as demonstrated by an enzyme-linked immunosorbent assay) and bactericidal activity were inhibited by de-N-acetylated MBPS and re-N-acetylated MBPS, which indicate thatN-propionyl groups are not obligatory determinants for binding. The results of affinity selection from a preparation ofN-Pr MBPS and matrix-assisted laser desorption ionization-time of flight mass spectroscopic analysis indicated that the minimal epitope recognized by the MAb is a MBPS disaccharide containing one de-N-acetylated residue. Thus, the bacterial capsular epitope recognized by this bactericidal, nonautoreactive, anti-group-B MAb likely contains de-N-acetyl residues.
Regulation of Type III Secretion Hierarchy of Translocators and Effectors in Attaching and Effacing Bacterial Pathogens
Authors: Deng Wanyin , Li Yuling , Hardwidge Philip R. , Frey Elizabeth A. , Pfuetzner Richard A. , Lee Sansan , Gruenheid Samantha , Strynakda Natalie C. J. , Puente Jose L. , Finlay B. Brett 
Published: March 2005

ABSTRACT

Human enteropathogenic
Escherichia coli
(EPEC), enterohemorrhagic
E. coli
(EHEC), and the mouse pathogen
Citrobacter rodentium
(CR) belong to the family of attaching and effacing (A/E) bacterial pathogens. They possess the locus of enterocyte effacement (LEE) pathogenicity island, which encodes a type III secretion system. These pathogens secrete a number of proteins into culture media, including type III effector proteins and translocators that are required for the translocation of effectors into host cells. Preliminary evidence indicated that the LEE-encoded SepL and Rorf6/SepD may form a molecular switch that controls the secretion of translocators and effectors in CR. Here, we show that SepL and SepD indeed perform this function in A/E pathogens such as EHEC and EPEC. Their
sepL
and
sepD
mutants do not secrete translocators but exhibit enhanced secretion of effectors. We demonstrate that SepL and SepD interact with each other and that both SepL and SepD are localized to the bacterial membranes. Furthermore, we demonstrate that culture media influence the type III secretion profile of EHEC, EPEC, and CR and that low-calcium concentrations inhibit secretion of translocators but promote the secretion of effectors, similar to effects on type III secretion by mutations in
sepL
and
sepD
. However, the secretion profile of the
sepD
and
sepL
mutants is not affected by these culture conditions. Collectively, our results suggest that SepL and SepD not only are necessary for efficient translocator secretion in A/E pathogens but also control a switch from translocator to effector secretion by sensing certain environmental signals such as low calcium.
Lipopolysaccharide Preparation Extracted fromPorphyromonas gingivalisLipoprotein-Deficient Mutant Shows a Marked Decrease in Toll-Like Receptor 2-Mediated Signaling
Authors: Asai Yasuyuki , Hashimoto Masahito , Fletcher Hansel M. , Miyake Kensuke , Akira Shizuo , Ogawa Tomohiko 
Published: March 2005

ABSTRACTWe recently demonstrated that a new PG1828-encoded lipoprotein (PG1828LP) was able to be separated from aPorphyromonas gingivalislipopolysaccharide (LPS) preparation, and we found that it exhibited strong cell activation, similar to that ofEscherichia coliLPS, through a Toll-like receptor 2 (TLR2)-dependent pathway. In order to determine the virulence of PG1828LP toward cell activation, we generated a PG1828-deficient mutant ofP. gingivalisstrain 381 by allelic exchange mutagenesis using anermF-ermAMantibiotic resistance cassette. A highly purified preparation of LPS from a PG1828-deficient mutant (ΔPG1828-LPS) showed nearly the same ladder-like patterns in silver-stained gels as a preparation of LPS from a wild-type strain (WT-LPS), as well asLimulusamoebocyte lysate activities that were similar to those of the WT-LPS preparation. However, the ability of the ΔPG1828-LPS preparation to activate NF-κB in TLR2-expressing cells was markedly attenuated. Cytokine production by human gingival fibroblasts was also decreased in response to the ΔPG1828-LPS preparation in comparison with the WT-LPS preparation, and the activity was comparable to the stimulation of highly purified lipid A ofP. gingivalisby TLR4. Further, lethal toxicity was rarely observed following intraperitoneal injection of the PG1828-deficient mutant into mice compared to that with the wild-type strain, while the ΔPG1828-LPS preparation showed no lethal toxicity. Taken together, these results clearly indicate that PG1828LP plays an essential role in inflammatory responses and may be a major virulence factor ofP. gingivalis.
The Innate Immune System Is Activated by Stimulation of Vaginal Epithelial Cells withStaphylococcus aureusand Toxic Shock Syndrome Toxin 1
Authors: Peterson Marnie L. , Ault Kevin , Kremer Mary J. , Klingelhutz Aloysius J. , Davis Catherine C. , Squier Christopher A. , Schlievert Patrick M. 
Published: March 2005

ABSTRACTDespite knowledge of the effects of toxic shock syndrome (TSS) toxin 1 (TSST-1) on the adaptive immune system, little is known about stimulation of the innate immune system, particularly epithelial cells. This study investigated the interactions of TSSStaphylococcus aureusand TSST-1 with human vaginal epithelial cells (HVECs) and porcine mucosal surfaces. When cocultured with HVECs for 6 h, TSSS. aureusMN8 proliferated, formed aggregates on the HVEC surfaces, and produced exotoxins. Receptor binding studies showed that35S-TSST-1 bound to 5 × 104receptors per HVEC, with saturation at 15 min. Affymetrix Human GeneChip U133A microarray analysis determinedS. aureusMNSM (100 bacteria/HVEC) caused at least twofold up- or down-regulation of 410 HVEC genes by 6 h; these data were also confirmed withS. aureusMN8. TSST-1 (100 μg/ml) caused up- or down-regulation of 2,386 HVEC genes by 6 h. In response toS. aureus, the HVEC genes most up-regulated compared to those in controls were those coding for chemokines or cytokines—MIP-3α, 478-fold; GRO-α, 26-fold; GRO-β, 14-fold; and GRO-γ, 30-fold—suggesting activation of innate immunity. TSST-1 also caused up-regulation of chemokine/cytokine genes. Chemokine/cytokine gene up-regulation was confirmed by enzyme-linked immunosorbent assays measuring the corresponding proteins induced byS. aureusand TSST-1.S. aureusMN8, when incubated with porcine vaginal tissue, increased the flux of35S-TSST-1 across the mucosal surface. This was accompanied by influx of lymphocytes into the upper layers of the tissue. These data suggest innate immune system activation through epithelial cells, reflected in chemokine/cytokine production and influx of lymphocytes, may cause changes in vaginal mucosa permeability, facilitating TSST-1 penetration.
Increased Expression of Interleukin-5 (IL-5), IL-13, and Tumor Necrosis Factor Alpha Genes in Intestinal Lymph Cells of Sheep Selected for Enhanced Resistance to Nematodes during Infection withTrichostrongylus colubriformis
Authors: Pernthaner Anton , Cole Sally-Ann , Morrison Lilian , Hein Wayne R. 
Published: March 2005

ABSTRACTCytokine gene expression in cells migrating in afferent and efferent intestinal lymph was monitored for extended time periods in individual sheep experimentally infected with the nematodeTrichostrongylus colubriformis. Animals from stable selection lines with increased levels of either genetic resistance (R) or susceptibility (S) to nematode infection were used. Genes for interleukin-5 (IL-5), IL-13, and tumor necrosis factor alpha (TNF-α), but not for IL-4, IL-10, or gamma interferon (IFN-γ), were consistently expressed at higher levels in both afferent and efferent lymph cells of R sheep than in S sheep. However, only minor differences were observed in the surface phenotypes and antigenic and mitogenic responsiveness of cells in intestinal lymph between animals from the two selection lines. The IL-4 and IL-10 genes were expressed at higher levels in afferent lymph cells than in efferent lymph cells throughout the course of the nematode infection in animals of both genotypes, while the proinflammatory TNF-α gene was relatively highly expressed in both lymph types. These relationships notwithstanding, expression of the IL-10 and TNF-α genes declined significantly in afferent lymph cells but not in efferent lymph cells during infection. Collectively, the results showed that R-line sheep developed a strong polarization toward a Th2-type cytokine profile in immune cells migrating in lymph from sites where the immune response to nematodes was initiated, although the IFN-γ gene was also expressed at moderate levels. Genes or alleles that predispose an animal to develop this type of response appear to have segregated with the R selection line and may contribute to the increased resistance of these animals.
Yersinia pestisV Protein Epitopes Recognized by CD4 T Cells
Authors: Parent Michelle A. , Berggren Kiera N. , Mullarky Isis K. , Szaba Frank M. , Kummer Lawrence W. , Adamovicz Jeffrey J. , Smiley Stephen T. 
Published: March 2005

ABSTRACTPneumonic plague, an often-fatal disease for which no vaccine is presently available, results from pulmonary infection by the bacteriumYersinia pestis. TheY. pestisV protein is a promising vaccine candidate, as V protein immunizations confer to mice significant protection against aerosolizedY. pestis. CD4 T cells play central roles during vaccine-primed immune responses, but their functional contributions toY. pestisvaccines have yet to be evaluated and optimized. Toward that end, we report here the identification of three distinct epitopes within theY. pestisV protein that activate CD4 T cells in C57BL/6 mice. To our knowledge, these are the first identified CD4 T-cell epitopes in anyY. pestisprotein. The epitopes are restricted by the I-Abclass II major histocompatibility complex molecule and are fully conserved betweenY. pestis,Yersinia pseudotuberculosis, andYersinia enterocolitica. Immunizing mice with a V protein-containing vaccine or with short peptides containing the identified epitopes primes antigen-specific production of interleukin 2 and gamma interferon by CD4 T cells upon their restimulation in vitro. Consistent with prior studies documenting protective roles for CD4 T cells duringY. enterocoliticainfection, vaccinating mice with a 16-amino-acid peptide encoding one of the epitopes suffices to protect against an otherwise lethalY. enterocoliticachallenge. The identification of these epitopes will permit quantitative assessments of V-specific CD4 T cells, thereby enabling researchers to evaluate and optimize the contribution of these cells to vaccine-primed protection against pneumonic plague.
Natural History of Gastric Mucosal Cytokine Expression inHelicobacter pyloriGastritis in Mongolian Gerbils
Authors: Yamaoka Yoshio , Yamauchi Kazuyoshi , Ota Hiroyoshi , Sugiyama Atsushi , Ishizone Satoshi , Graham David Y. , Maruta Fukuto , Murakami Maki , Katsuyama Tsutomu 
Published: March 2005

ABSTRACTData regarding the chronological changes in gastric mucosal cytokines in the different phases ofHelicobacter pyloriinfection are unavailable. We examined Mongolian gerbils for up to 52 weeks afterH. pylori(ATCC 43504) inoculation. Levels of mRNAs of mucosal cytokines (interleukin-1β [IL-1β], gamma interferon [IFN-γ], IL-4, IL-6, and IL-10) were assessed using real-time reverse transcription-PCR. Starting 26 weeks afterH. pyloriinoculation, two clinicohistologic patterns appeared: gastric ulcers in 32% and hyperplastic polyps in 68% of gerbils. High levels of mucosal IL-1β mRNA were observed early in the infection, reaching maximum at 4 weeks and then rapidly declining. Mucosal IFN-γ mRNA also reached maximal levels at 4 weeks but remained high thereafter. Both IL-1β and IFN-γ mRNA levels were consistently higher in the pyloric mucosa than in the fundic mucosa. In contrast, IL-4, IL-6, and IL-10 mRNA levels peaked at 8 to 26 weeks and levels were similar in the pyloric mucosa and the fundic mucosa. IFN-γ mRNA levels were significantly higher in gerbils with ulcers than in those with hyperplastic polyps (median IFN-γ/glyceraldehyde-3-phosphate dehydrogenase ratio × 100,000 = 650 versus 338, respectively [antrum], and 172 versus 40, respectively [corpus]) (P< 0.05). We propose that the different outcomes (e.g., ulcers or hyperplastic polyps) might relate to imbalances among cytokines.
Role of YadA, Ail, and Lipopolysaccharide in Serum Resistance ofYersinia enterocoliticaSerotype O:3
Authors: Biedzka-Sarek Marta , Venho Reija , Skurnik Mikael 
Published: March 2005

ABSTRACTComplement attack is a host strategy leading to elimination of pathogens.Yersinia enterocoliticaexpresses several potential complement resistance factors: the outer membrane proteins YadA and Ail as well as lipopolysaccharide (LPS). To study the contribution of these factors to the survival ofY. enterocoliticaserotype O:3 in nonimmune human serum, we constructed 23 mutant strains ofY. enterocoliticaO:3 expressing different combinations of YadA, Ail, LPS O antigen, and LPS outer core. Survival of bacteria was analyzed in normal serum (with functional classical, lectin, and alternative complement activation pathways) and EGTA-Mg-treated serum (only alternative pathway functional). Kinetic killing tests revealed that the most potent single-serum resistance factor needed for long-term survival was YadA; Ail was also indispensable, but it provided short-term survival and delayed the bacterial killing. On the contrary, the LPS O antigen and outer core, when in combination with YadA, Ail, or both, had a minor and often negative effect on serum resistance. Bacteria in the exponential phase of growth were more resistant to serum killing than stationary-phase bacteria. After exposing bacteria to EGTA-Mg-treated serum, O antigen could prevent deposition of covalently bound C3b on bacteria at 3 min of incubation, even as a single factor. At later time points (15 and 30 min) it had to be accompanied by YadA, Ail, and outer core. In normal serum, the bacteria were less resistant to C3b deposition. However, no direct correlation between the C3 deposition pattern and bacterial resistance was observed.
Fluid- or Surface-Phase Human Salivary Scavenger Protein gp340 Exposes Different Bacterial Recognition Properties
Authors: Loimaranta V. , Jakubovics N. S. , Hytönen J. , Finne J. , Jenkinson H. F. , Strömberg N. 
Published: March 2005

ABSTRACT

Salivary scavenger receptor cysteine-rich protein gp340 aggregates streptococci and other bacteria as part of the host innate defense system at mucosal surfaces. In this article, we have investigated the properties of fluid-phase gp340 and hydroxylapatite surface-adsorbed gp340 in aggregation and adherence, respectively, of viridans group streptococci (e.g.,
Streptococcus gordonii
and
Streptococcus mutans)
, non-viridans group streptococci (e.g.,
Streptococcus pyogenes
and
Streptococcus suis
), and oral
Actinomyces
. Fluid-phase gp340 and surface-phase gp340 bioforms were differentially recognized by streptococci, which formed three phenotypic groupings according to their modes of interaction with gp340. Group I streptococci were aggregated by and adhered to gp340, and group II streptococci preferentially adhered to surface-bound gp340, while group III streptococci were preferentially aggregated by gp340. Each species of
Streptococcus
tested was found to contain strains representative of at least two of these gp340 interaction groupings. The gp340 interaction modes I to III and sugar specificities of gp340 binding strains coincided for several species. Many gp340 interactions were sialidase sensitive, and each of the interaction modes (I to III) for
S. gordonii
was correlated with a variant of sialic acid specificity. Adherence of
S. gordonii
DL1 (Challis) to surface-bound gp340 was dependent upon expression of the sialic acid binding adhesin Hsa. However, aggregation of cells by fluid-phase gp340 was independent of Hsa and involved SspA and SspB (antigen I/II family) polypeptides. Conversely, both gp340-mediated aggregation and adherence of
S. mutans
NG8 involved antigen I/II polypeptide. Deletion of the
mga
virulence regulator gene in
S. pyogenes
resulted in increased cell aggregation by gp340. These results suggest that salivary gp340 recognizes different bacterial receptors according to whether gp340 is present in the fluid phase or surface bound. This phase-associated differential recognition by gp340 of streptococcal species of different levels of virulence and diverse origins may mediate alternative host responses to commensal or pathogenic bacterial phenotypes.