bluuebunny/crossref_metadata_2025_split huggingface dataset:
Th1 Cytokines Facilitate CD8-T-Cell-Mediated Early Resistance to Infection withMycobacterium tuberculosisin Old Mice
Authors: Vesosky Bridget , Flaherty David K. , Turner Joanne 
Published: May 2006

ABSTRACTNumerous immunological defects begin to emerge as an individual ages, the consequence of which is heightened susceptibility to infectious diseases. Despite this decline in immune function, old mice display an early transient resistance toMycobacterium tuberculosisinfection in the lung, which is dependent on CD8 T cells and gamma interferon (IFN-γ) production. In this study, we investigated the mechanism of resistance by examining the CD8-T-cell phenotype and function in old naïve andM. tuberculosis-infected mice. Pulmonary CD8 T cells from naïve old mice expressed cell surface markers of memory in addition to receptors for several Th1 cytokines. Stimulation of lung cells from naïve old mice with a combination of Th1 cytokines (interleukin-2 [IL-2], IL-12, and IL-18) resulted in nonspecific production of IFN-γ by memory CD8 T cells. Following aerosol infection withM. tuberculosis, the lungs of old mice contained significantly more IL-12, IL-18, and IFN-γ than the lungs of young mice contained. Together, these data demonstrate that the increased and early production of Th1 cytokines in the lungs ofM. tuberculosis-infected old mice, in combination with CD8 T cells that can nonspecifically produce IFN-γ, leads to transient control ofM. tuberculosisgrowth in the lungs of old mice. Further characterization of this mechanism should provide essential information regarding the aging immune system and should contribute to the development of novel strategies to decrease the morbidity and mortality of the aging population associated with infectious diseases.
Heterogeneity in Tandem Octanucleotides within
Haemophilus influenzae
Lipopolysaccharide Biosynthetic Gene
losA
Affects Serum Resistance
Authors: Erwin Alice L. , Bonthuis Paul J. , Geelhood Jennifer L. , Nelson Kevin L. , McCrea Kirk W. , Gilsdorf Janet R. , Smith Arnold L. 
Published: May 2006

ABSTRACT

Haemophilus influenzae
is subject to phase variation mediated by changes in the length of simple sequence repeat regions within several genes, most of which encode either surface proteins or enzymes involved in the synthesis of lipopolysaccharides (LPS). The translational repeat regions that have been described thus far all consist of tandemly repeated tetranucleotides. We describe an octanucleotide repeat region within a putative LPS biosynthetic gene,
losA
. Approximately 20 percent of nontypeable
H. influenzae
strains contain copies of
losA
and
losB
in a genetic locus flanked by
infA
and
ksgA
. Of 30 strains containing
losA
at this site, 24 contained 2 tandem copies of the octanucleotide CGAGCATA, allowing full-length translation of
losA
(on), and 6 strains contained 3, 4, 6, or 10 tandem copies (
losA
off). For a serum-sensitive strain, R3063, with
losA
off (10 repeat units), selection for serum-resistant variants yielded a heterogeneous population in which colonies with increased serum resistance had
losA
on (2, 8, or 11 repeat units), and colonies with unchanged sensitivity to serum had 10 repeats. Inactivation of
losA
in strains R3063 and R2846 (strain 12) by insertion of the
cat
gene decreased the serum resistance of these strains compared to
losA
-on variants and altered the electrophoretic mobility of LPS. We conclude that expression of
losA
, a gene that contributes to LPS structure and affects serum resistance, is determined by octanucleotide repeat variation.
Mycobacterium tuberculosisBinding to Human Surfactant Proteins A and D, Fibronectin, and Small Airway Epithelial Cells under Shear Conditions
Authors: Hall-Stoodley Luanne , Watts Gayle , Crowther Joy E. , Balagopal Ashwin , Torrelles Jordi B. , Robison-Cox James , Bargatze Robert F. , Harmsen Allen G. , Crouch Erika C. , Schlesinger Larry S. 
Published: May 2006

ABSTRACTA crucial step in infection is the initial attachment of a pathogen to host cells or tissue.Mycobacterium tuberculosishas evolved multiple strategies for establishing an infection within the host. The pulmonary microenvironment contains a complex milieu of pattern recognition molecules of the innate immune system that play a role in the primary response to inhaled pathogens. Encounters ofM. tuberculosiswith these recognition molecules likely influence the outcome of the bacillus-host interaction. Here we use a novel fluid shear assay to investigate the binding ofM. tuberculosisto innate immune molecules that are produced by pulmonary epithelial cells and are thought to play a role in the lung innate immune response. Virulent and attenuatedM. tuberculosisstrains bound best to immobilized human fibronectin (FN) and surfactant protein A (SP-A) under this condition. Binding under fluid shear conditions was more consistent and significant compared to binding under static conditions. Soluble FN significantly increased the adherence of both virulent and attenuatedM. tuberculosisstrains to human primary small airway epithelial cells (SAEC) under fluid shear conditions. In contrast, SP-A and SP-D effects on bacterial adherence to SAEC differed between the two strains. The use of a fluid shear model to simulate physiological conditions within the lung and select for high-affinity binding interactions should prove useful for studies that investigate interactions betweenM. tuberculosisand host innate immune determinants.
Macrophage Migration Inhibitory Factor Contributes to Host Defense against AcuteTrypanosoma cruziInfection
Authors: Reyes José L. , Terrazas Luis I. , Espinoza Bertha , Cruz-Robles David , Soto Virgilia , Rivera-Montoya Irma , Gómez-García Lorena , Snider Heidi , Satoskar Abhay R. , Rodríguez-Sosa Miriam 
Published: May 2006

ABSTRACTMacrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is involved in the host defense against several pathogens. Here we used MIF−/−mice to determine the role of endogenous MIF in the regulation of the host immune response againstTrypanosoma cruziinfection. MIF−/−mice displayed high levels of blood and tissue parasitemia, developed severe heart and skeletal muscle immunopathology, and succumbed toT. cruziinfection faster than MIF+/+mice. The enhanced susceptibility of MIF−/−mice toT. cruziwas associated with reduced levels of proinflammatory cytokines, such as tumor necrosis factor alpha, interleukin-12 (IL-12), IL-18, gamma interferon (IFN-γ), and IL-1β, in their sera and reduced production of IL-12, IFN-γ, and IL-4 by spleen cells during the early phase of infection. At all time points, antigen-stimulated splenocytes from MIF+/+and MIF−/−mice produced comparable levels of IL-10. MIF−/−mice also produced significantly less Th1-associated antigen-specific immunoglobulin G2a (IgG2a) throughout the infection, but both groups produced comparable levels of Th2-associated IgG1. Lastly, inflamed hearts fromT. cruzi-infected MIF−/−mice expressed increased transcripts for IFN-γ, but fewer for IL-12 p35, IL-12 p40, IL-23, and inducible nitric oxide synthase, compared to MIF+/+mice. Taken together, our findings show that MIF plays a role in controlling acuteT. cruziinfection.
Infection of Human Dendritic Cells with aMycobacterium tuberculosis sigEMutant Stimulates Production of High Levels of Interleukin-10 but Low Levels of CXCL10: Impact on the T-Cell Response
Authors: Giacomini Elena , Sotolongo Ambar , Iona Elisabetta , Severa Martina , Remoli Maria Elena , Gafa Valerie , Lande Roberto , Fattorini Lanfranco , Smith Issar , Manganelli Riccardo , Coccia Eliana M. 
Published: May 2006

ABSTRACTTheMycobacterium tuberculosisgenome encodes 13 sigma factors. We have previously shown that mutations in some of these transcriptional activators renderM. tuberculosissensitive to various environmental stresses and can attenuate the virulence phenotype. In this work, we focused on extracytoplasmic factor σEand studied the effects induced by the deletion of its structural gene (sigE) in the infection of human monocyte-derived dendritic cells (MDDC). We found that the wild-typeM. tuberculosisstrain (H37Rv), thesigEmutant (ST28), and the complemented strain (ST29) were able to infect dendritic cells (DC) to similar extents, although at 4 days postinfection a reduced ability to grow inside MDDC was observed for thesigEmutant ST28. After mycobacterium capture, the majority of MDDC underwent full maturation and expressed both inflammatory cytokines, such as tumor necrosis factor alpha, and the regulatory cytokines interleukin-12 (IL-12), IL-18, and beta interferon (IFN-β). Conversely, a higher level of production of IL-10 was observed in ST28-infected MDDC compared to H37Rv- or ST29-infected cell results. However, in spite of the presence of IL-10, supernatants from ST28-infected DC induced IFN-γ production by T cells similarly to those from H37Rv-infected DC culture. On the other hand, IL-10 impaired CXCL10 production insigEmutant-infected DC and, indeed, its neutralization restored CXCL10 secretion. In line with these results, supernatants from ST28-infected cells showed a decreased capability to recruit CXCR3+CD4+T cells compared to those obtained from H37Rv-infected DC culture. Thus, our findings suggest that thesigEmutant-induced secretion of IL-10 inhibits CXCL10 expression and, in turn, the recruitment of activated-effector cells involved in the formation of granulomas.
Identification of a Novel Antigen ofSchistosoma mansoniShared withPlasmodium falciparumand Evaluation of Different Cross-Reactive Antibody Subclasses Induced by Human Schistosomiasis and Malaria
Authors: Pierrot Christine , Wilson Shona , Lallet Hélène , Lafitte Sophia , Jones Frances M. , Daher Wassim , Capron Monique , Dunne David W. , Khalife Jamal 
Published: May 2006

ABSTRACTPlasmodium falciparumandSchistosoma mansoniare often found in human coinfections, and cross-reactive antibodies to different components of the two parasites have been detected. In this work, we identified a cross-reactiveS. mansonigene product, referred to as SmLRR, that seems to belong to the leucine-rich repeat protein family. Comparative analysis of SmLRR revealed 57% similarity with a putative gene product encoded in theP. falciparumgenome. Antibodies to SmLRR were found in experimental infections and in bothS. mansoni- andP. falciparum-infected individuals. Correlative analysis of human anti-SmLRR responses in Kenya and Uganda suggested that malaria and schistosomiasis drive the immunoglobulin G3 (IgG3) and IgG4 isotypes, respectively, against SmLRR, suggesting that there is differential regulation of cross-reactive isotypes depending on the infection. In addition, the levels of anti-SmLRR IgG4, but not the levels of IgG3, correlated positively with the intensity ofS. mansoniinfection.
Differences in Gene Expression between the Classical and El Tor Biotypes of
Vibrio cholerae
O1
Authors: Beyhan Sinem , Tischler Anna D. , Camilli Andrew , Yildiz Fitnat H. 
Published: May 2006

ABSTRACT

Differences in whole-genome expression patterns between the classical and El Tor biotypes of
Vibrio cholerae
O1 were determined under conditions that induce virulence gene expression in the classical biotype. A total of 524 genes (13.5% of the genome) were found to be differentially expressed in the two biotypes. The expression of genes encoding proteins required for biofilm formation, chemotaxis, and transport of amino acids, peptides, and iron was higher in the El Tor biotype. These gene expression differences may contribute to the enhanced survival capacity of the El Tor biotype in environmental reservoirs. The expression of genes encoding virulence factors was higher in the classical than in the El Tor biotype. In addition, the
vieSAB
genes, which were originally identified as regulators of
ctxA
transcription, were expressed at a fivefold higher level in the classical biotype. We determined the VieA regulon in both biotypes by transcriptome comparison of wild-type and
vieA
deletion mutant strains. VieA predominantly regulates gene expression in the classical biotype; 401 genes (10.3% of the genome), including those encoding proteins required for virulence, exopolysaccharide biosynthesis, and flagellum production as well as those regulated by σ
E
, are differentially expressed in the classical
vieA
deletion mutant. In contrast, only five genes were regulated by VieA in the El Tor biotype. A large fraction (20.8%) of the genes that are differentially expressed in the classical versus the El Tor biotype are controlled by VieA in the classical biotype. Thus, VieA is a major regulator of genes in the classical biotype under virulence gene-inducing conditions.
Rhamnolipids Are Virulence Factors That Promote Early Infiltration of Primary Human Airway Epithelia byPseudomonas aeruginosa
Authors: Zulianello Laurence , Canard Coralie , Köhler Thilo , Caille Dorothée , Lacroix Jean-Silvain , Meda Paolo 
Published: May 2006

ABSTRACTThe opportunistic bacteriumPseudomonas aeruginosacauses chronic respiratory infections in cystic fibrosis and immunocompromised individuals. Bacterial adherence to the basolateral domain of the host cells and internalization are thought to participate inP. aeruginosapathogenicity. However, the mechanism by which the pathogen initially modulates the paracellular permeability of polarized respiratory epithelia remains to be understood. To investigate this mechanism, we have searched for virulence factors secreted byP. aeruginosathat affect the structure of human airway epithelium in the early stages of infection. We have found that only bacterial strains secreting rhamnolipids were efficient in modulating the barrier function of an in vitro-reconstituted human respiratory epithelium, irrespective of their release of elastase and lipopolysaccharide. In contrast to previous reports, we document thatP. aeruginosawas not internalized by epithelial cells. We further report that purified rhamnolipids, applied on the surfaces of the epithelia, were sufficient to functionally disrupt the epithelia and to promote the paracellular invasion of rhamnolipid-deficientP. aeruginosa. The mechanism involves the incorporation of rhamnolipids within the host cell membrane, leading to tight-junction alterations. The study provides direct evidence for a hitherto unknown mechanism whereby the junction-dependent barrier of the respiratory epithelium is selectively altered by rhamnolipids.
Role for Dendritic Cells in Immunoregulation during Experimental Vaginal Candidiasis
Authors: LeBlanc Dana M. , Barousse Melissa M. , Fidel Paul L. 
Published: May 2006

ABSTRACTVulvovaginal candidiasis (VVC) caused by the commensal organismCandida albicansremains a significant problem among women of childbearing age, with protection against and susceptibility to infection still poorly understood. While cell-mediated immunity by CD4+Th1-type cells is protective against most forms of mucosal candidiasis, no protective role for adaptive immunity has been identified against VVC. This is postulated to be due to immunoregulation that prohibits a more profoundCandida-specific CD4+T-cell response against infection. The purpose of this study was to examine the role of dendritic cells (DCs) in the induction phase of the immune response as a means to understand the initiation of the immunoregulatory events. Immunostaining of DCs in sectioned murine lymph nodes draining the vagina revealed a profound cellular reorganization with DCs becoming concentrated in the T-cell zone throughout the course of experimental vaginalCandidainfection consistent with cell-mediated immune responsiveness. However, analysis of draining lymph node DC subsets revealed a predominance of immunoregulation-associated CD11c+B220+plasmacytoid DCs (pDCs) under both uninfected and infected conditions. Staining of vaginal DCs showed the presence of both DEC-205+and pDCs, with extension of dendrites into the vaginal lumen of infected mice in close contact withCandida. Flow cytometric analysis of draining lymph node DC costimulatory molecules and activation markers from infected mice indicated a lack of upregulation of major histocompatibility complex class II, CD80, CD86, and CD40 during infection, consistent with a tolerizing condition. Together, the results suggest that DCs are involved in the immunoregulatory events manifested during a vaginalCandidainfection and potentially through the action of pDCs.
Topical Application of
Escherichia coli
-Vectored Vaccine as a Simple Method for Eliciting Protective Immunity
Authors: Zhang Jianfeng , Shi Zhongkai , Kong Fan-kun , Jex Edward , Huang Zhigang , Watt James M. , Van Kampen Kent R. , Tang De-chu C. 
Published: May 2006

ABSTRACT

We report here that animals can be protected against lethal infection by
Clostridium tetani
cells and
Bacillus anthracis
spores following topical application of intact particles of live or γ-irradiated
Escherichia coli
vectors overproducing tetanus and anthrax antigens, respectively. Cutaneous γδT cells were rapidly recruited to the administration site. Live
E. coli
cells were not found in nonskin tissues after topical application, although fragments of
E. coli
DNA were disseminated transiently. Evidence suggested that intact
E. coli
particles in the outer layer of skin may be disrupted by a γδT-cell-mediated innate defense mechanism, followed by the presentation of
E. coli
ligand-adjuvanted intravector antigens to the immune system and rapid degradation of
E. coli
components. The nonreplicating
E. coli
vector overproducing an exogenous immunogen may foster the development of a new generation of vaccines that can be manufactured rapidly and administered noninvasively in a wide variety of disease settings.
The ABC Transporter Protein OppA Provides Protection against Experimental
Yersinia pestis
Infection
Authors: Tanabe Mikio , Atkins Helen S. , Harland David N. , Elvin Stephen J. , Stagg Anthony J. , Mirza Osman , Titball Richard W. , Byrne Bernadette , Brown Katherine A. 
Published: May 2006

ABSTRACT

The identification of
Yersinia pestis
as a potential bioterrorism agent and the emergence of antibiotic-resistant strains have highlighted the need for improved vaccines and treatments for plague. The aim of this study was to evaluate the potential for ATP-binding cassette (ABC) transporter proteins to be exploited as novel vaccines against plague. Western blotting of ABC transporter proteins using sera from rabbits immunized with killed whole
Y. pestis
cells or human convalescent-phase sera identified four immunologically reactive proteins: OppA, PstS, YrbD, and PiuA. Mice immunized with these proteins developed antibody to the immunogen. When the immunized mice were challenged with
Y. pestis
, the OppA-immunized mice showed an increased time to death compared to other groups, and protection appeared to correlate with the level of immunoglobulin G antibody to OppA.
Differential Genome Contents of Nontypeable
Haemophilus influenzae
Strains from Adults with Chronic Obstructive Pulmonary Disease
Authors: Fernaays Matthew M. , Lesse Alan J. , Sethi Sanjay , Cai Xueya , Murphy Timothy F. 
Published: May 2006

ABSTRACT

Haemophilus influenzae
is an important cause of otitis media in children and lower respiratory infection in adults with chronic obstructive pulmonary disease (COPD). Patients with COPD experience periodic exacerbations that are associated with acquisition of new bacterial strains. However, not every strain acquisition is associated with exacerbation. To test the hypothesis that genetic differences among strains account for differences in pathogenic potential, a microarray consisting of 4,992 random 1.5- to 3-kb genomic fragments of an exacerbation strain was constructed. Competitive hybridization was performed using six strains associated with exacerbation as well as five strains associated with asymptomatic colonization. Seven sequences that were absent in all five colonization strains and present in at least two exacerbation strains were identified. One such sequence was a previously unreported gene with high homology to the meningococcal immunoglobulin A (IgA) protease gene, which is distinct from the previously described
H. influenzae
IgA protease. To assess the distribution of the seven sequences among well-characterized strains of
H. influenzae
, 59 exacerbation strains and 73 asymptomatic colonization strains were screened by PCR for the presence of these sequences. The presence or absence of any single sequence was not significantly associated with exacerbations of COPD. However, logistic regression and subgroup analysis identified combinations of the presence and absence of genes that are associated with exacerbations. These results indicate that patterns of genes are associated with the ability of strains of
H. influenzae
to cause exacerbations of COPD, supporting the concept that differences in pathogenic potential are based in part on genomic differences among infecting strains, not merely host factors.
Borrelia burgdorferi
OspC Protein Required Exclusively in a Crucial Early Stage of Mammalian Infection
Authors: Tilly Kit , Krum Jonathan G. , Bestor Aaron , Jewett Mollie W. , Grimm Dorothee , Bueschel Dawn , Byram Rebecca , Dorward David , VanRaden Mark J. , Stewart Philip , Rosa Patricia 
Published: May 2006

ABSTRACT

This study demonstrates a strict temporal requirement for a virulence determinant of the Lyme disease spirochete
Borrelia burgdorferi
during a unique point in its natural infection cycle, which alternates between ticks and small mammals. OspC is a major surface protein produced by
B. burgdorferi
when infected ticks feed but whose synthesis decreases after transmission to a mammalian host. We have previously shown that spirochetes lacking OspC are competent to replicate in and migrate to the salivary glands of the tick vector but do not infect mice. Here we assessed the timing of the requirement for OspC by using an
ospC
mutant complemented with an unstable copy of the
ospC
gene and show that
B. burgdorferi
's requirement for OspC is specific to the mammal and limited to a critical early stage of mammalian infection. By using this unique system, we found that most bacterial reisolates from mice persistently infected with the initially complemented
ospC
mutant strain no longer carried the wild-type copy of
ospC
. Such spirochetes were acquired by feeding ticks and migrated to the tick salivary glands during subsequent feeding. Despite normal behavior in ticks, these
ospC
mutant spirochetes did not infect naive mice.
ospC
mutant spirochetes from persistently infected mice also failed to infect naive mice by tissue transplantation. We conclude that OspC is indispensable for establishing infection by
B. burgdorferi
in mammals but is not required at any other point of the mouse-tick infection cycle.
Global Gene Expression Profiling of the Asymptomatic BacteriuriaEscherichia coliStrain 83972 in the Human Urinary Tract
Authors: Roos Viktoria , Klemm Per 
Published: May 2006

ABSTRACTUrinary tract infections (UTIs) are an important health problem worldwide, with many million cases each year.Escherichia coliis the most common organism causing UTIs in humans. The asymptomatic bacteriuriaE. colistrain 83972 is an excellent colonizer of the human urinary tract, where it causes long-term bladder colonization. The strain has been used for prophylactic purposes in patients prone to more severe and recurrent UTIs. For this study, we used DNA microarrays to monitor the expression profile of strain 83972 in the human urinary tract. Significant differences in expression levels were seen between the in vivo expression profiles of strain 83972 in three patients and the corresponding in vitro expression profiles in lab medium and human urine. The data revealed an in vivo lifestyle of microaerobic growth with respiration of nitrate coupled to degradation of sugar acids and amino acids, with no signs of attachment to host tissues. Interestingly, genes involved in NO protection and metabolism showed significant up-regulation in the patients. This is one of the first studies to address bacterial whole-genome expression in humans and the first study to investigate global gene expression of anE. colistrain in the human urinary tract.