bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiviral Actions of Interferons
Authors: Samuel Charles E. 
Published: July 2002

SUMMARYTremendous progress has been made in understanding the molecular basis of the antiviral actions of interferons (IFNs), as well as strategies evolved by viruses to antagonize the actions of IFNs. Furthermore, advances made while elucidating the IFN system have contributed significantly to our understanding in multiple areas of virology and molecular cell biology, ranging from pathways of signal transduction to the biochemical mechanisms of transcriptional and translational control to the molecular basis of viral pathogenesis. IFNs are approved therapeutics and have moved from the basic research laboratory to the clinic. Among the IFN-induced proteins important in the antiviral actions of IFNs are the RNA-dependent protein kinase (PKR), the 2′,5′-oligoadenylate synthetase (OAS) and RNase L, and the Mx protein GTPases. Double-stranded RNA plays a central role in modulating protein phosphorylation and RNA degradation catalyzed by the IFN-inducible PKR kinase and the 2′-5′-oligoadenylate-dependent RNase L, respectively, and also in RNA editing by the IFN-inducible RNA-specific adenosine deaminase (ADAR1). IFN also induces a form of inducible nitric oxide synthase (iNOS2) and the major histocompatibility complex class I and II proteins, all of which play important roles in immune response to infections. Several additional genes whose expression profiles are altered in response to IFN treatment and virus infection have been identified by microarray analyses. The availability of cDNA and genomic clones for many of the components of the IFN system, including IFN-α, IFN-β, and IFN-γ, their receptors, Jak and Stat and IRF signal transduction components, and proteins such as PKR, 2′,5′-OAS, Mx, and ADAR, whose expression is regulated by IFNs, has permitted the generation of mutant proteins, cells that overexpress different forms of the proteins, and animals in which their expression has been disrupted by targeted gene disruption. The use of these IFN system reagents, both in cell culture and in whole animals, continues to provide important contributions to our understanding of the virus-host interaction and cellular antiviral response.
Differential Sensitivities ofChlamydia trachomatisStrains to Inhibitory Effects of Gamma Interferon
Authors: Morrison Richard P. 
Published: July 2002

ABSTRACTGamma interferon (IFN-γ) is an important cytokine in host defense against chlamydial infection. An in vitro cell culture system was used to show that IFN-γ inhibition of chlamydial growth, as determined by diminished recovery of infectious elementary bodies, differed markedly among chlamydial strains. These differences in sensitivity among chlamydial strains to IFN-γ-mediated inhibition may profoundly influence the clinical outcome of infection.
Epithelial Cell Adherence Mediated by the Enterotoxigenic
Escherichia coli
Tia Protein
Authors: Mammarappallil Joseph G. , Elsinghorst Eric A. 
Published: July 2002

ABSTRACT

In vitro studies have shown that enterotoxigenic
Escherichia coli
(ETEC) strains are capable of invading cultured epithelial cells derived from the human ileum and colon. Two separate invasion loci (
tia
and
tib
) have previously been isolated from the classical ETEC strain
H10407
. The
tia
locus has been shown to direct the synthesis of Tia, a 25-kDa outer membrane protein. Tia is sufficient to confer the adherence and invasion phenotypes on laboratory stains of
E. coli
, suggesting that this protein is an adhesin and invasin. Here we report the purification of Tia and characterize its biological activity. Tia was purified by electroelution of outer membrane proteins that had been separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Purified Tia was labeled with biotin and then shown to bind to HCT8 human ileocecal epithelial cells in a specific and saturable manner. Polyclonal anti-Tia antiserum blocked this binding. These results show that Tia acts as an adhesin. Polyclonal anti-Tia antiserum also inhibited invasion of recombinant
E. coli
bearing
tia
clones, indirectly suggesting that Tia may also act as an invasin. We predict Tia to contain eight transmembrane amphipathic β-sheets with four loops that are exposed on the surface of the bacterial cell. A peptide corresponding to 19 residues in one of the four predicted surface-exposed loops inhibits Tia-mediated epithelial cell invasion. Seeding HCT8 cells on wells coated with purified Tia reduced Tia-mediated epithelial cell invasion. Together, these results indicate that Tia is an invasin and adhesin that binds a specific receptor on HCT8 cells.
OppA of
Listeria monocytogenes
, an Oligopeptide-Binding Protein Required for Bacterial Growth at Low Temperature and Involved in Intracellular Survival
Authors: Borezee Elise , Pellegrini Elisabeth , Berche Patrick 
Published: July 2002

ABSTRACT

We identified a new oligopeptide permease operon in the pathogen
Listeria monocytogenes
. This
opp
operon consists of five genes (
oppA, oppB, oppC, oppD
, and
oppF
) and displays the same genetic organization as those of several bacterial species. The first gene of this operon,
oppA
, encodes a 62-kDa protein sharing 33% identity with OppA of
Bacillus subtilis
and is expressed predominantly during exponential growth. The function of
oppA
was studied by constructing an
oppA
deletion mutant. The phenotype analysis of this mutant revealed that OppA mediates the transport of oligopeptides and is required for bacterial growth at low temperature. The wild-type phenotype was restored by complementing the mutant with
oppA
. We also found that OppA is involved in intracellular survival in macrophages and in bacterial growth in organs of mice infected with
L. monocytogenes
, although the level of virulence was not altered in the mutant. These results show the major role of OppA in the uptake of oligopeptides and the pleiotropic effects of this oligopeptide-binding protein on the behavior of this pathogen in the environment and in its host.
Infectious CTXΦ and the Vibrio Pathogenicity Island Prophage in
Vibrio mimicus
: Evidence for Recent Horizontal Transfer between
V. mimicus
and
V. cholerae
Authors: Boyd E. Fidelma , Moyer Kathryn E. , Shi Lei , Waldor Matthew K. 
Published: July 2002

ABSTRACT

Vibrio mimicus
differs from
Vibrio cholerae
in a number of genotypic and phenotypic traits but like
V. cholerae
can give rise to diarrheal disease. We examined clinical isolates of
V. mimicus
for the presence of CTXΦ, the lysogenic filamentous bacteriophage that carries the cholera toxin genes in epidemic
V. cholerae
strains. Four
V. mimicus
isolates were found to contain complete copies of CTXΦ. Southern blot analyses revealed that
V. mimicus
strain PT5 contains two CTX prophages integrated at different sites within the
V. mimicus
genome whereas
V. mimicus
strains PT48, 523-80, and 9583 each contain tandemly arranged copies of CTXΦ. We detected the replicative form of CTXΦ, pCTX, in all four of these
V. mimicus
isolates. The CTX prophage in strain PT5 was found to produce infectious CTXΦ particles. The nucleotide sequences of CTXΦ genes
orfU
and
zot
from
V. mimicus
strain PT5 and
V. cholerae
strain N16961 were identical, indicating contemporary horizontal transfer of CTXΦ between these two species. The receptor for CTXΦ, the toxin-coregulated pilus, which is encoded by another lysogenic filamentous bacteriophage, VPIΦ, was also present in the CTXΦ-positive
V. mimicus
isolates. The nucleotide sequences of VPIΦ genes
aldA
and
toxT
from
V. mimicus
strain PT5 and
V. cholerae
N16961 were identical, suggesting recent horizontal transfer of this phage between
V. mimicus
and
V. cholerae
. In
V. mimicus
, the vibrio pathogenicity island prophage was integrated in the same chromosomal attachment site as in
V. cholerae
. These results suggest that
V. mimicus
may be a significant reservoir for both CTXΦ and VPIΦ and may play an important role in the emergence of new toxigenic
V. cholerae
isolates.
Microgravity as a Novel Environmental Signal Affecting
Salmonella enterica
Serovar Typhimurium Virulence
Authors: Nickerson Cheryl A. , Ott C. Mark , Mister Sarah J. , Morrow Brian J. , Burns-Keliher Lisa , Pierson Duane L. 
Published: July 2002

ABSTRACT

The effects of spaceflight on the infectious disease process have only been studied at the level of the host immune response and indicate a blunting of the immune mechanism in humans and animals. Accordingly, it is necessary to assess potential changes in microbial virulence associated with spaceflight which may impact the probability of in-flight infectious disease. In this study, we investigated the effect of altered gravitational vectors on
Salmonella
virulence in mice.
Salmonella enterica
serovar Typhimurium grown under modeled microgravity (MMG) were more virulent and were recovered in higher numbers from the murine spleen and liver following oral infection compared to organisms grown under normal gravity. Furthermore, MMG-grown salmonellae were more resistant to acid stress and macrophage killing and exhibited significant differences in protein synthesis than did normal-gravity-grown cells. Our results indicate that the environment created by simulated microgravity represents a novel environmental regulatory factor of
Salmonella
virulence.
Immune Response against a Cross-Reactive Epitope on the Heat Shock Protein 60 Homologue ofHelicobacter pylori
Authors: Yamaguchi Hiroyuki , Osaki Takako , Kai Masanori , Taguchi Haruhiko , Kamiya Shigeru 
Published: July 2002

ABSTRACTWe previously established a monoclonal antibody (MAb), designated H9, which reacts with the heat shock protein 60 (HSP60) homologue ofHelicobacter pylorias well as with other bacterial and human HSP60s. To determine the importance of a cross-reactive epitope onH. pyloriHSP60 inH. pyloriimmunopathogenesis, we performed (i) mapping of an epitope onH. pyloriHSP60 recognized by the H9 MAb, (ii) analysis of immunoglobulin G responses of patients with or withoutH. pyloriinfection to its epitope region, and (iii) studies of the protective effect of immunization with its epitope region onH. pyloriinfection in mice. The epitope recognized by the H9 MAb was mapped to the sequence of amino acids 189 to 203 (VEGMQFDRGYLSPYF) on theH. pyloriHSP60 molecule. It was confirmed that the synthesized peptide designated pH9 was recognized by the H9 MAb. Enzyme-linked immunosorbent assay analysis showed that patients withH. pyloriinfection (n= 349) had significantly lower titers of pH9 antibody than did uninfected patients (n= 200) (P< 0.001), but this was not the case with purifiedH. pyloriHSP60 recombinantEscherichia coliGroEL, or recombinant human HSP60. In C57BL/6 mice immunized with the pH9 peptide with Freund's complete adjuvant (FCA), the number ofH. pyloriorganisms colonizing the stomach was significantly lower than that in mice immunized with pCont plus FCA (P< 0.0001) or FCA only (P< 0.005). The results suggest that the immune response to the cross-reactive epitope (pH9 region) onH. pyloriHSP60 is unique and might be associated with protection againstH. pyloriinfection.
Administration of Endotoxin Associated with Lipopolysaccharide Tolerance Protects Mice against Fungal Infection
Authors: Rayhane Naïma , Fitting Catherine , Lortholary Olivier , Dromer Francoise , Cavaillon Jean-Marc 
Published: July 2002

ABSTRACTLipopolysaccharide (LPS) pretreatment of mice resulted in a significantly enhanced survival after disseminatedCryptococcus neoformansinfection. The survival was associated with reduced fungal burden in tissues. LPS-pretreated mice had lower levels of cytokines in blood, spleen, and lungs and higher levels in brain. Pentoxifylline abolished the beneficial effect of LPS pretreatment.
Improved Innate Immunity of Endotoxin-Tolerant Mice Increases Resistance toSalmonella entericaSerovar Typhimurium Infection despite Attenuated Cytokine Response
Authors: Lehner Martin D. , Ittner Josepha , Bundschuh Daniela S. , van Rooijen Nico , Wendel Albrecht , Hartung Thomas 
Published: July 2002

ABSTRACTDuring infection with gram-negative bacteria, exposure of immune cells to lipopolysaccharide (LPS) from the bacterial cell membrane induces a rapid cytokine response which is essential for the activation of host defenses against the invading pathogens. Administration of LPS to mice induces a state of hyporesponsiveness, or tolerance, characterized by reduced cytokine production upon subsequent LPS challenge. In the model of experimentalSalmonella entericaserovar Typhimurium infection of mice, we assessed the question of whether complete LPS tolerance induced by repetitive doses of LPS interfered with cytokine production and host defense against gram-negative bacteria. Although production of various cytokines in response to serovar Typhimurium was attenuated by LPS pretreatment, LPS-tolerant mice showed improved antibacterial activity, evidenced by a prolongation of survival and a continuously lower bacterial load. We attribute this protective effect to three independent mechanisms. (i) Peritoneal accumulation of leukocytes in the course of LPS pretreatment accounted for enhanced defense against serovar Typhimurium during the first 6 h of infection but not for decreased bacterial load in late-stage infection. (ii) LPS-tolerant mice had an increased capacity to recruit neutrophilic granulocytes during infection. (iii) LPS-tolerant mice showed threefold-increased Kupffer cell numbers, enhanced phagocytic activity of the liver, and strongly improved clearance of blood-borne serovar Typhimurium. These results demonstrate that despite attenuated cytokine response, acquired LPS tolerance is associated with enhanced resistance to infections by gram-negative bacteria and that this effect is mainly mediated by improved effector functions of the innate immune system.
Tick Salivary Gland Extract Inhibits Killing ofBorrelia afzeliiSpirochetes by Mouse Macrophages
Authors: Kuthejlová Marie , Kopecký Jan , Štěpánová Gabriela , Macela Aleš 
Published: July 2002

ABSTRACTSalivary gland extract (SGE) fromIxodes ricinusticks inhibited the killing ofBorrelia afzeliispirochetes by murine macrophages. SGE also reduced the production of two major defense molecules of phagocytes, superoxide and nitric oxide. It is likely that the suppression of macrophage microbicidal mechanisms contributes to the inhibitory effect of tick saliva on the killing ofB. afzeliispirochetes, thus facilitating the transmission of this important pathogen.
Urethral Cytokine and Immune Responses in
Chlamydia trachomatis
-Infected Males
Authors: Pate Mitchell S. , Hedges Spencer R. , Sibley Don A. , Russell Michael W. , Hook Edward W. , Mestecky Jiri 
Published: July 2002

ABSTRACT

Penile urethral swabs collected from PCR-confirmed
Chlamydia trachomatis
-infected,
C. trachomatis
-uninfected, and non-
C. trachomatis
-infected, nongonococcal urethritis-infected males were analyzed for cytokine, total immunoglobulin (Ig), and specific antibody levels by enzyme-linked immunosorbent assay. Differential cellular components of the swab transport medium were also enumerated for the same groups. Although low, the levels of
C. trachomatis
-specific IgA and IgG antibodies and interleukin 8 cytokine were significantly higher in
C. trachomatis
-infected individuals. There were no significant differences in the levels of seven additional cytokines evaluated.
Characterization of the Adhesin of
Escherichia coli
F18 Fimbriae
Authors: Smeds A. , Hemmann K. , Jakava-Viljanen M. , Pelkonen S. , Imberechts H. , Palva A. 
Published: July 2002

ABSTRACT

Previous research has suggested that the adhesin encoded by the F18 fimbrial operon in
Escherichia coli
is either the FedE or FedF protein. In this work, we show that anti-FedF antibodies, unlike anti-FedE serum, were able to inhibit
E. coli
adhesion to porcine enterocytes. Moreover, specific adhesion to enterocytes was shown with purified FedF-maltose binding protein.
Pneumolysin Is the Main Inducer of Cytotoxicity to Brain Microvascular Endothelial Cells Caused by
Streptococcus pneumoniae
Authors: Zysk Gregor , Schneider-Wald Barbara Katharina , Hwang Jae Hyuk , Bejo Levente , Kim Kwang Sik , Mitchell Timothy J. , Hakenbeck Regine , Heinz Hans-Peter 
Published: July 2002

ABSTRACT

In pneumococcal meningitis it is assumed that bacteria cross the blood-brain barrier (BBB), which consists mainly of cerebral endothelial cells. The effect of
Streptococcus pneumoniae
on the BBB was investigated with an in vitro BBB model using a human brain microvascular endothelial cell line (HBMEC) and primary cultures of bovine brain microvascular endothelial cells (BBMEC). Within a few hours of incubation with pneumococci, rounding and detachment of the HBMEC were observed, and the transendothelial electrical resistance of the BBMEC monolayer decreased markedly. An
S. pneumoniae
mutant deficient in pneumolysin did not affect the integrity of the endothelial cell monolayer. Neither cell wall fragments nor isolated pneumococcal cell walls induced changes of endothelial cell morphology. However, purified pneumolysin caused endothelial cell damage comparable to that caused by the viable pneumococci. The cell detachment was dependent on de novo protein synthesis and required the activities of caspase and tyrosine kinases. The results show that pneumolysin is an important component for damaging the BBB and may contribute to the entry of pneumococci into the cerebral compartment and to the development of brain edema in pneumococcal meningitis.
Functional Characterization of Streptococcal Pyrogenic Exotoxin J, a Novel Superantigen
Authors: McCormick John K. , Pragman Alexa A. , Stolpa John C. , Leung Donald Y. M. , Schlievert Patrick M. 
Published: July 2002

ABSTRACT

Streptococcal toxic shock syndrome (STSS) is a highly lethal, acute-onset illness that is a subset of invasive streptococcal disease. The majority of clinical STSS cases have been associated with the pyrogenic toxin superantigens (PTSAgs) streptococcal pyrogenic exotoxin A or C (SPE A or C), although cases have been reported that are not associated with either of these exotoxins. Recent genome sequencing projects have revealed a number of open reading frames that potentially encode proteins with similarity to SPEs A and C and to other PTSAgs. Here, we describe the cloning, expression, purification, and functional characterization of a novel exotoxin termed streptococcal pyrogenic exotoxin J (SPE J). Purified recombinant SPE J (rSPE J) expressed from
Escherichia coli
stimulated the expansion of both rabbit splenocytes and human peripheral blood lymphocytes, preferentially expanded human T cells displaying Vβ2, -3, -12, -14, and -17 on their T-cell receptors, and was active at concentrations as low as 5 × 10
−6
μg/ml. Furthermore, rSPE J induced fevers in rabbits and was lethal in two models of STSS. Biochemically, SPE J had a predicted molecular weight of 24,444 and an isoelectric point of 7.7 and lacked the ability to form the cystine loop structure characteristic of many PTSAgs. SPE J shared 19.6, 47.1, 38.8, 18.1, 19.6, and 24.4% identity with SPEs A, C, G, and H, streptococcal superantigen, and streptococcal mitogenic exotoxin Z-2, respectively, and was immunologically cross-reactive with SPE C. The characterization of a seventh functional streptococcal PTSAg raises important questions relating to the evolution of the streptococcal superantigens.
Signaling by Toll-Like Receptor 2 and 4 Agonists Results in Differential Gene Expression in Murine Macrophages
Authors: Hirschfeld Matthew , Weis Janis J. , Toshchakov Vladimir , Salkowski Cindy A. , Cody M. Joshua , Ward Dawn C. , Qureshi Nilofer , Michalek Suzanne M. , Vogel Stefanie N. 
Published: July 2002

ABSTRACTLipopolysaccharide (LPS) derived from the periodontal pathogenPorphyromonas gingivalishas been reported to differ structurally and functionally from enterobacterial LPS. These studies demonstrate that in contrast to protein-free enterobacterial LPS, a similarly purified preparation ofP. gingivalisLPS exhibited potent Toll-like receptor 2 (TLR2), rather than TLR4, agonist activity to elicit gene expression and cytokine secretion in murine macrophages and transfectants. More importantly, TLR2 stimulation by thisP. gingivalisLPS preparation resulted in differential expression of a panel of genes that are normally induced in murine macrophages byEscherichia coliLPS. These data suggest that (i)P. gingivalisLPS does not signal through TLR4 and (ii) signaling through TLR2 and through TLR4 differs quantitatively and qualitatively. Our data support the hypothesis that the shared signaling pathways elicited by TLR2 and by TLR4 agonists must diverge in order to account for the distinct patterns of inflammatory gene expression.
Salmonella entericaSerovar Typhimurium Induces Cell Death in Bovine Monocyte-Derived Macrophages by EarlysipB-Dependent and DelayedsipB-Independent Mechanisms
Authors: Santos Renato L. , Tsolis Renée M. , Bäumler Andreas J. , Smith Roger , Adams L. Garry 
Published: July 2002

ABSTRACTIt was previously demonstrated thatSalmonella entericaserovar Typhimurium induces cell death with features of apoptosis in murine macrophages. Mice infected withSalmonellaserovar Typhimurium develop systemic disease without diarrhea, whereas the infection in cattle and in humans is localized and characterized by diarrhea. Considering these clinical disease expression differences between mice and cattle, we investigated whether serovar Typhimurium is cytotoxic for bovine macrophages. Macrophages infected with serovar Typhimurium grown in the logarithmic phase quickly underwent cell death. Macrophages infected with stationary-phase cultures or with a mutant lackingsipBunderwent no immediate cell death but did develop delayed cytotoxicity, undergoing cell death between 12 and 18 h postinfection. Both pathways were temporarily blocked by the general caspase inhibitor Z-VAD-Fmk and by the caspase 1 inhibitor Z-YVAD-Fmk. Comparisons of macrophages from cattle naturally resistant or susceptible to intracellular pathogens indicated no differences between these two genetic backgrounds in terms of susceptibility to serovar Typhimurium-induced cell death. We conclude thatSalmonellaserovar Typhimurium induces cell death in bovine macrophages by two distinct mechanisms, earlysipB-mediated and delayedsipB-independent mechanisms.