bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Regulation of Cytokine Production by CD1d-Restricted NKT Cells in Response to Superantigen Staphylococcal Enterotoxin B Exposure
Authors: Ragin Melanie J. , Sahu Nisebita , August Avery 
Published: December 2005

ABSTRACTNKT cells are a heterogeneous population characterized by the ability to rapidly produce cytokines, such as interleukin 2 (IL-2), IL-4, and gamma interferon (IFN-γ) in response to infections by viruses, bacteria, and parasites. The bacterial superantigen staphylococcal enterotoxin B (SEB) interacts with T cells bearing the Vβ3, -7, or -8 T-cell receptors, inducing their expansion and cytokine secretion, leading to death in some cases due to cytokine poisoning. The majority of NKT cells bear the Vβ7 or -8 T-cell receptor, suggesting that they may play a role in regulating this response. Using mice lacking NKT cells (CD1d−/−and Jα18−/−mice), we set out to identify the role of these cells in T-cell expansion, cytokine secretion, and toxicity induced by exposure to SEB. We find that Vβ8+CD4+T-cell populations similarly expand in wild-type (WT) and NKT cell-null mice and that NKT cells did not regulate the secretion of IL-2. By contrast, these cells positively regulated the secretion of IL-4 and IFN-γ production and negatively regulated the secretion of tumor necrosis factor alpha (TNF-α). However, this negative regulation of TNF-α secretion by NKT cells provides only a minor protective effect on SEB-mediated shock in WT mice compared to mice lacking NKT cells. These data suggest that NKT cells may regulate the nature of the cytokine response to exposure to the superantigen SEB and may act as regulatory T cells during exposure to this superantigen.
Identification of a Surface Protein of
Streptococcus suis
and Evaluation of Its Immunogenic and Protective Capacity in Pigs
Authors: Li Yuanyi , Martinez Gabriela , Gottschalk Marcelo , Lacouture Sonia , Willson Philip , Dubreuil J. Daniel , Jacques Mario , Harel Josee 
Published: December 2005

ABSTRACT

A
Streptococcus suis
surface protein reacting with convalescent-phase sera from pigs clinically infected by
S. suis
type 2 was identified. The apparent 110-kDa protein, designated Sao, exhibits typical features of membrane-anchored surface proteins of gram-positive bacteria, such as a signal sequence and an LPVTG membrane anchor motif. In spite of high identity with the partially sequenced genomes of
S. suis
Canadian strain 89/1591 and European strain P1/7, Sao does not share significant homology with other known sequences. However, a conserved avirulence domain that is often found in plant pathogens has been detected. Electron microscopy using an Sao-specific antiserum has confirmed the surface location of the Sao protein on
S. suis
. The Sao-specific antibody reacts with cell lysates of 28 of 33
S. suis
serotypes and 25 of 26 serotype 2 isolates in immunoblots, suggesting its high conservation in
S. suis
species. The immunization of piglets with recombinant Sao elicits a significant humoral antibody response. However, the antibody response is not reflected in protection of pigs that are intratracheally challenged with a virulent strain in our conventional vaccination model.
Identification of CsrC and Characterization of Its Role in Epithelial Cell Invasion in
Salmonella enterica
Serovar Typhimurium
Authors: Fortune Doreen R. , Suyemoto Mitsu , Altier Craig 
Published: December 2005

ABSTRACT

The csr regulatory system of
Salmonella
regulates the expression of the genes of
Salmonella
pathogenicity island 1 (SPI1) required for the invasion of epithelial cells. This system consists of the posttranscriptional regulator CsrA and an untranslated regulatory RNA, CsrB, that opposes the action of CsrA. Here we identify and characterize the role of a second regulatory RNA, CsrC, whose ortholog was discovered previously in
Escherichia coli
. We show that a mutant of
csrC
has only mild defects in invasion and the expression of SPI1 genes, as does a mutant of
csrB
, but that a double
csrB csrC
mutant is markedly deficient in these properties, suggesting that the two regulatory RNAs play redundant roles in the control of invasion. We further show that CsrC, like CsrB, is controlled by the BarA/SirA two-component regulator but that a
csrB csrC
mutant exhibits a loss of invasion equivalent to that of a
barA
or
sirA
mutant, indicating that much of the effect of BarA/SirA on invasion functions through its control of CsrB and CsrC. In addition to their control by BarA/SirA, each regulatory RNA is also controlled by other components of the csr system. The loss of
csrB
was found to increase the level of CsrC by sevenfold, while the loss of
csrC
increased CsrB by nearly twofold. Similarly, the overexpression of
csrA
increased CsrC by nearly 11-fold and CsrB by 3-fold and also significantly increased the stability of both RNAs.
T-Helper-2 Cytokine Responses to Sj97 Predict Resistance to Reinfection withSchistosoma japonicum
Authors: Leenstra Tjalling , Acosta Luz P. , Wu Hai-Wei , Langdon Gretchen C. , Solomon Julie S. , Manalo Daria L. , Su Li , Jiz Mario , Jarilla Blanca , Pablo Archie O. , McGarvey Stephen T. , Olveda Remigio M. , Friedman Jennifer F. , Kurtis Jonathan D. 
Published: December 2005

ABSTRACTAlthough schistosomiasis is effectively treated with Praziquantel, rapid reinfection with rebound morbidity precludes effective control based on chemotherapy alone and justifies current efforts to develop vaccines for these parasites. Using a longitudinal treatment-reinfection study design with 616 participants 7 to 30 years of age, we evaluated the relationship between cytokine responses toSchistosoma japonicumsoluble adult worm extract (SWAP), Sj97, Sj22.6, and Sj67, measured 4 weeks after treatment with Praziquantel, and resistance to reinfection in a population from Leyte, The Philippines, whereS. japonicumis endemic.S. japonicumtransmission was high: 54.8% and 91.1% were reinfected within 6 and 18 months, respectively. A Th2 bias in the following cytokine ratios, interleukin-4 (IL-4)/IL-12, IL-5/IL-12, IL-13/IL-12, IL-4/gamma-IFN (IFN-γ), IL-5/IFN-γ, and IL-13/IFN-γ, in response to SWAP predicted a 1.4- to 2.9-month longer time to reinfection (P< 0.05) and a 27 to 55% lower intensity of reinfection (P< 0.05). Similarly, a Th2 bias in response to Sj97 predicted a 1.6- to 2.2-month longer time to reinfection (P< 0.05) and a 30 to 41% lower intensity of reinfection (P< 0.05). Only a high IL-5/IL-10 ratio in response to Sj22.6 predicted a 3.0-month-longer time to reinfection (P= 0.03). Cytokine responses to Sj67 were not associated with protection. In a large population-based treatment-reinfection study we found that Th2 responses to SWAP and Sj97 consistently predicted resistance to reinfection. These findings underscore Th2-type immune responses as central in human resistance toS. japonicumand support Sj97 as a leading vaccine candidate for this parasite.
Complement and Fc Function Are Required for Optimal Antibody Prophylaxis againstPneumocystis cariniiPneumonia
Authors: Wells Jesse , Haidaris Constantine G. , Wright Terry W. , Gigliotti Francis 
Published: December 2005

ABSTRACTPneumocystis cariniiis an opportunistic fungal pathogen that causesP. cariniipneumonia (PCP) in the immunocompromised host. We investigated the role of antibody Fc-mediated function in passive prophylaxis against the development of PCP in SCID mice. By comparison of anti-mouseP. cariniiimmunoglobulin G1 monoclonal antibody (MAb) 4F11(G1) and its F(ab′)2 derivative in an intranasal immunoprophylaxis model, we determined that Fc-mediated function is required for maximum effect of this antibody. Comparison of efficacy of antibody prophylaxis in SCID mice depleted of complement to that in nondepleted mice demonstrated that complement fixation by MAb 4F11(G1) is also necessary for optimal effect of passively administered antibody, although residual protection was observed in complement-depleted SCID mice. The necessity of complement for optimal PCP prophylaxis by MAb 4F11(G1) suggests that complement may play a role in antibody-mediated protection against development of PCP.
Effect of Inactivation of the Global Oxidative Stress Regulator
oxyR
on the Colonization Ability of
Escherichia coli
O1:K1:H7 in a Mouse Model of Ascending Urinary Tract Infection
Authors: Johnson James R. , Clabots Connie , Rosen Henry 
Published: December 2005

ABSTRACT

To survive within the host urinary tract,
Escherichia coli
strains that cause urinary tract infection (UTI) presumably must overcome powerful oxidant stresses, including the oxygen-dependent killing mechanisms of neutrophils. Accordingly, we assessed the global oxygen stress regulator OxyR of
Escherichia coli
as a possible virulence factor in UTI by determining the impact of
oxyR
inactivation on experimental urovirulence in CBA/J and C57BL (both wild-type and p47
phox−/−
) mice. The
oxyR
and
oxyS
genes of wild-type
E. coli
strain Ec1a (O1:K1:H7) were replaced with a kanamycin resistance cassette to produce an
oxyRS
mutant. During in vitro growth in broth or human urine, the
oxyRS
mutant exhibited the same log-phase growth rate (broth) and plateau density (broth and urine) as Ec1a, despite its prolonged lag phase (broth) or initial decrease in concentration (urine). The mutant, and
oxyRS
mutants of other wild-type ExPEC strains, exhibited significantly increased in vitro susceptibility to inhibition by H
2
O
2
, which, like the altered growth kinetics observed with
oxyRS
inactivation, were reversed by restoration of
oxyR
on a multiple-copy-number plasmid. In CBA/J mice, Ec1a significantly outcompeted its
oxyRS
mutant (by >1 log
10
) in urine, bladder, and kidney cultures harvested 48 h after perurethral inoculation of mice, whereas an
oxyR
-complemented mutant exhibited equal or greater colonizing ability than that of the parent. Although C57BL mice were less susceptible to experimental UTI than CBA/J mice, wild-type and p47
phox−/−
C57BL mice were similarly susceptible, and the
oxyR
mutant of Ec1a was similarly attenuated in C57BL mice, regardless of the p47
phox
genotype, as in CBA/J mice. Within the
E. coli
Reference collection, 94% of strains were positive for
oxyR
. These findings fulfill the second and third of Koch's molecular postulates for
oxyR
as a candidate virulence-facilitating factor in
E. coli
and indicate that
oxyR
is a broadly prevalent potential target for future preventive interventions against UTI due to
E. coli
. They also suggest that neutrophil phagocyte oxidase is not critical for defense against
E. coli
UTI and that the major oxidative stresses against which OxyR protects
E. coli
within the host milieu are not phagocyte derived.
Roles of Macrophages and Neutrophils in the Early Host Response toBacillus anthracisSpores in a Mouse Model of Infection
Authors: Cote Christopher K. , Van Rooijen Nico , Welkos Susan L. 
Published: December 2005

ABSTRACTThe development of new approaches to combat anthrax requires that the pathogenesis and host response toBacillus anthracisspores be better understood. We investigated the roles that macrophages and neutrophils play in the progression of infection byB. anthracisin a mouse model. Mice were treated with a macrophage depletion agent (liposome-encapsulated clodronate) or with a neutrophil depletion agent (cyclophosphamide or the rat anti-mouse granulocyte monoclonal antibody RB6-8C5), and the animals were then infected intraperitoneally or by aerosol challenge with fully virulent, ungerminatedB. anthracisstrain Ames spores. The macrophage-depleted mice were significantly more susceptible to the ensuing infection than the saline-pretreated mice, whereas the differences observed between the neutropenic mice and the saline-pretreated controls were generally not significant. We also found that augmenting peritoneal neutrophil populations before spore challenge did not increase resistance of the mice to infection. In addition, the bacterial load in macrophage-depleted mice was significantly greater and appeared significantly sooner than that observed with the saline-pretreated mice. However, the bacterial load in the neutropenic mice was comparable to that of the saline-pretreated mice. These data suggest that, in our model, neutrophils play a relatively minor role in the early host response to spores, whereas macrophages play a more dominant role in early host defenses against infection byB. anthracisspores.
Two Domains within theMycoplasma hyopneumoniaeCilium Adhesin Bind Heparin
Authors: Jenkins Cheryl , Wilton Jody L. , Minion F. Chris , Falconer Linda , Walker Mark J. , Djordjevic Steven P. 
Published: December 2005

ABSTRACTMycoplasma hyopneumoniaeis the causative agent of porcine enzootic pneumonia, a chronic and economically significant respiratory disease that affects swine production worldwide.M. hyopneumoniaeadheres to and adversely affects the function of ciliated epithelial cells of the respiratory tract, and the cilium adhesin (Mhp183, P97) is intricately but not exclusively involved in this process. Although binding of pathogenic bacteria to glycosaminoglycans is a recognized step in pathogenesis, knowledge of glycosaminoglycan-binding proteins inM. hyopneumoniaeis lacking. However, heparin and other sulfated polysaccharides are known to block the binding ofM. hyopneumoniaeto purified swine respiratory cilia. In this study, four regions within the cilium adhesin were examined for the ability to bind heparin. Cilium adhesin fragments comprising 653 amino acids of the N terminus and 301 amino acids of the C terminus (containing two repeat regions, R1 and R2) were cloned and expressed. These fragments bound heparin in a dose-dependent and saturable manner with physiologically significant binding affinities of 0.27 ± 0.02 μM and 1.89 ± 0.33 μM, respectively. Heparin binding of both fragments was strongly inhibited by the sulfated polysaccharides fucoidan and mucin but not by chondroitin sulfate B. When the C-terminal repeat regions R1 and R2 were cloned separately and expressed, heparin-binding activity was lost, suggesting that both regions are required for heparin binding. The ability of the cilium adhesin to bind heparin indicates that this molecule plays a multifunctional role in the adherence ofM. hyopneumoniaeto host respiratory surfaces and therefore has important implications with respect to the pathogenesis of this organism.
CpG-Oligodeoxynucleotide Is a Potent Adjuvant with anEntamoeba histolyticaGal-Inhibitable Lectin Vaccine against Amoebic Liver Abscess in Gerbils
Authors: Ivory Catherine P. A. , Keller Kathy , Chadee Kris 
Published: December 2005

ABSTRACTThe protozoan parasiteEntamoeba histolyticacauses invasive amoebiasis characterized by amoebic dysentery and liver abscesses (ALA). TheE. histolyticagalactose/N-acetyl-d-galactosamine-inhibitable lectin (Gal-lectin), an immunogenic surface molecule involved in colonization and invasion, is a promising vaccine candidate against amoebiasis. Gal-lectin is known to induce Th1 cytokines in macrophages and spleen cells in vitro, and a Th1 response is thought to be protective against ALA. In this study, we report the use of cytosine guanine oligodeoxynucleotide (CpG-ODN) as adjuvant to augment Th1 responses against Gal-lectin in the gerbil model of ALA. Gerbils were vaccinated intramuscularly with the native Gal-lectin plus CpG-ODN or a paired non-CpG control GpC-ODN, and control gerbils received CpG-ODN alone. One week after the last boost gerbils were challenged intrahepatically with 106amoebae. Gerbils receiving CpG-ODN as adjuvant with Gal-lectin were completely protected against the development of ALA, whereas 50% of gerbils receiving GpC-ODN and Gal-lectin developed ALA and 85% of controls developed ALA. Stronger lymphoproliferation in response to the Gal-lectin and higher prechallenge titers of serum Gal-lectin-specific antibodies, capable of blocking amoebic adherence, were observed when CpG-ODN was used as adjuvant. Gerbils vaccinated with CpG-ODN and Gal-lectin also had significantly higher levels of gamma interferon, interleukin-12 (IL-12), and IL-2 mRNA than controls. These data indicate that CpG-ODN can enhance the Th1 responses, which improve the protective effects of Gal-lectin. This is the first report of the use of CpG as a potent Th1 adjuvant with Gal-lectin to increase protection against ALA formation.
Plasmid Interleukin-23 (IL-23), but Not Plasmid IL-27, Enhances the Protective Efficacy of a DNA Vaccine againstMycobacterium tuberculosisInfection
Authors: Wozniak Teresa M. , Ryan Anthony A. , Triccas James A. , Britton Warwick J. 
Published: December 2005

ABSTRACTProtection against intracellular pathogens such asMycobacterium tuberculosisrequires the development of Th1-like T-cell responses. This in turn is dependent on the pattern of cytokine produced from dendritic cells (DCs) after infection. Three heterodimeric cytokines, interleukin-12 (IL-12), IL-23, and IL-27, as well as IL-18, contribute to the differentiation and expansion of naive CD4+T cells. In this study we compared the effects of plasmids expressing both chains of IL-12, IL-23, or IL-27 as adjuvants for DNA immunization againstM. tuberculosisinfection. The genes encoding p19 and p40 chains of IL-23 or EBI3 and p28 chains of IL-27 were cloned on either side of a self-cleaving peptide from the FMDV2A protein. The secretion of functional cytokines from transfected cells was detected with bioassays. Supernatant from p2AIL-23-transfected cells induced the release of IL-17 from activated lymphocytes, confirming the presence of bioactive IL-23. Further, supernatant from p2AIL-27-transfected cells stimulated a significant increase in the proliferation of peptide-stimulated transgenic CD4+T cells. In initial experiments,M. tuberculosisinfection of DCs was more potent at inducing IL-12 and IL-23 secretion than infection with the vaccine strainMycobacterium bovisbacille Calmette-Guérin (BCG), and no significant upregulation of IL-27 was observed. Coimmunization of C57BL/6 mice with DNA expressingM. tuberculosisantigen 85B (Ag85B; DNA85B) and plasmids expressing IL-23 or IL-12 stimulated stronger Ag85B-specific T-cell proliferative and IFN-γ responses than DNA85B alone, whereas the addition of p2AIL-27 had no effect. Interestingly, DNA85B codelivered with p2AIL-12, but not p2AIL-23, reduced the immunoglobulin G antibody response. Both p2AIL-23 and p2AIL-12, but not p2AIL-27, enhanced the protective efficacy of DNA85B against aerosolM. tuberculosischallenge. Therefore, both p2AIL-23 and p2AIL-12 are valuable as cytokine adjuvants for increasing the protective antituberculosis immunity induced by DNA vaccines.
Dihydrolipoamide Acyltransferase Is Critical forMycobacterium tuberculosisPathogenesis
Authors: Shi Shuangping , Ehrt Sabine 
Published: December 2005

ABSTRACTMycobacterium tuberculosishas evolved to persist in host macrophages, where it faces a nutrient-poor environment and is exposed to oxidative and nitrosative stress. To defend itself against oxidative/nitrosative stress,M. tuberculosisexpresses an NADH-dependent peroxidase and peroxynitrite reductase that is encoded byahpC,ahpD,lpd, anddlaT. In addition to its central role in the peroxynitrite reductase complex,dlaT(Rv2215) also encodes the E2 component of pyruvate dehydrogenase. Here we demonstrate that inactivation ofdlaTin the chromosome of H37Rv resulted in a mutant (H37RvΔdlaT) that displayed phenotypes associated with DlaT's role in metabolism and in defense against nitrosative stress. The H37RvΔdlaTstrain showed retarded growth in vitro and was highly susceptible to killing by acidified sodium nitrite. Mouse macrophages readily killed intracellular H37RvΔdlaTorganisms, and in micedlaTwas required for full virulence.
Identification of the Insulin-Like Growth Factor II Receptor as a Novel Receptor for Binding and Invasion by
Listeria monocytogenes
Authors: Gasanov Uta , Koina Craig , Beagley Kenneth W. , Aitken R. John , Hansbro Philip M. 
Published: December 2005

ABSTRACT

The gram-positive bacterium
Listeria monocytogenes
causes a life-threatening disease known as listeriosis. The mechanism by which
L. monocytogenes
invades mammalian cells is not fully understood, but the processes involved may provide targets to prevent and treat listeriosis. Here, for the first time, we have identified the insulin-like growth factor II receptor (IGFIIR; also known as the cation-independent mannose 6-phosphate receptor
CI
M6PR or CD222) as a novel receptor for binding and invasion of
Listeria
species. Random peptide phage display was employed to select a peptide sequence by panning with immobilized
L. monocytogenes
cells; this peptide sequence corresponds to a sequence within the mannose 6-phosphate binding site of the IGFIIR. All
Listeria
spp. specifically bound the labeled peptide but not a control peptide, which was demonstrated using fluorescence spectrophotometry and fluorescence-activated cell sorting. Further evidence for binding of the receptor by
L. monocytogenes
and
L. innocua
was provided by affinity purification of the bovine IGFIIR from fetal calf serum by use of magnetic beads coated with cell preparations of
Listeria
spp. as affinity matrices. Adherence to and invasion of mammalian cells by
L. monocytogenes
was significantly inhibited by both the synthetic peptide and mannose 6-phosphate but not by appropriate controls. These observations indicate a role for the IGFIIR in the adherence and invasion of
L. monocytogenes
of mammalian cells, perhaps in combination with known mechanisms. Ligation of IGFIIR by
L. monocytogenes
may be a novel mechanism that contributes to the regulation of infectivity, possibly in combination with other mechanisms.
TheompAGene inChlamydia trachomatisDiffers in Phylogeny and Rate of Evolution from Other Regions of the Genome
Authors: Brunelle Brian W. , Sensabaugh George F. 
Published: December 2005

ABSTRACTStrains ofChlamydia trachomatisare classified into serovars based on nucleotide sequence differences inompA, the gene that encodes the major outer membrane protein. Phylogenetic characterization of strains based onompA, however, results in serovar groupings that are inconsistent with the distinguishing features ofC. trachomatispathobiology, e.g., tissue tropisms and disease presentation. We have compared nucleotide sequences at multiple sites distributed around the chlamydial genome from 18 strains representing 16 serovars; sampled regions included genes encoding housekeeping enzymes (totaling 2,073 bp), intergenic noncoding segments (1,612 bp), and a gene encoding a second outer membrane protein (porB; 1,023 bp), with theompAsequence (1,194 bp) used for reference. These comparative analyses revealed substantial variation in nucleotide substitution patterns among the sampled regions, with average pairwise sequence differences ranging from 0.15% for the housekeeping genes to 12.1% forompA. Phylogenetic characterization of the sampled genomic sequences yielded a strongly supported tree that divides the strains into groupings consistent withC. trachomatisbiology and which has a topology quite distinct from theompAtree. This phylogenetic incongruity can be accounted for by recombination of theompAgene between different genomic backgrounds. We found, however, no evidence of recombination within or between any of the sampled regions around theC. trachomatisgenome apart fromompA. Parallel analysis of published sequence data on four members of thepmpgene family are consistent with the phylogenetic analyses reported here.