bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced Susceptibility to Pulmonary Infection withBurkholderia cepaciainCftr−/−Mice
Authors: Sajjan Uma , Thanassoulis George , Cherapanov Vera , Lu Annie , Sjolin Carola , Steer Brent , Wu Yi Jun , Rotstein Ori D. , Kent Geraldine , McKerlie Colin , Forstner Janet , Downey Gregory P. 
Published: July 2002

ABSTRACTProgressive pulmonary infection is the dominant clinical feature of cystic fibrosis (CF), but the molecular basis for this susceptibility remains incompletely understood. To study this problem, we developed a model of chronic pneumonia by repeated instillation of a clinical isolate ofBurkholderia cepacia(genomovar III, ET12 strain), an opportunistic gram-negative bacterium, from a case of CF into the lungs ofCftrm1unc−/−(Cftr−/−) and congenicCftr+/+controls. Nine days after the last instillation, the CF transmembrane regulator knockout mice showed persistence of viable bacteria with chronic severe bronchopneumonia while wild-type mice remained healthy. The histopathological changes in the lungs of the susceptibleCftr−/−mice were characterized by infiltration of a mixed inflammatory-cell population into the peribronchiolar and perivascular spaces, Clara cell hyperplasia, mucus hypersecretion in airways, and exudation into alveolar airspaces by a mixed population of macrophages and neutrophils. An increased proportion of neutrophils was observed in bronchoalveolar lavage fluid from theCftr−/−mice, which, despite an increased bacterial load, demonstrated minimal evidence of activation. Alveolar macrophages fromCftr−/−mice also demonstrated suboptimal activation. These observations suggest that the pulmonary host defenses are compromised in lungs from animals with CF, as manifested by increased susceptibility to bacterial infection and lung injury. This murine model of chronic pneumonia thus reflects, in part, the situation in human patients and may help elucidate the mechanisms leading to defective host defense in CF.
Comparison of Virulence of
Legionella longbeachae
Strains in Guinea Pigs and U937 Macrophage-Like Cells
Authors: Doyle Robyn M. , Cianciotto Nicholas P. , Banvi Shaila , Manning Paul A. , Heuzenroeder Michael W. 
Published: July 2002

ABSTRACT

A guinea pig model of experimental legionellosis was established for assessment of virulence of isolates of
Legionella longbeachae
. The results showed that there were distinct virulence groupings of
L. longbeachae
serogroup 1 strains based on the severity of disease produced in this model. Statistical analysis of the animal model data suggests that Australian isolates of
L. longbeachae
may be inherently more virulent than non-Australian strains. Infection studies performed with U937 cells were consistent with the animal model studies and showed that isolates of this species were capable of multiplying within these phagocytic cells. Electron microscopy studies of infected lung tissue were also undertaken to determine the intracellular nature of
L. longbeachae
serogroup 1 infection. The data showed that phagosomes containing virulent
L. longbeachae
serogroup 1 appeared bloated, contained cellular debris and had an apparent rim of ribosomes while those containing avirulent
L. longbeachae
serogroup 1 were compact, clear and smooth.
Cellular and Humoral Immune Responses and Protection against Schistosomes Induced by a Radiation-Attenuated Vaccine in Chimpanzees
Authors: Eberl Matthias , Langermans Jan A. M. , Frost Patrice A. , Vervenne Richard A. , van Dam Govert J. , Deelder André M. , Thomas Alan W. , Coulson Patricia S. , Wilson R. Alan 
Published: July 2002

ABSTRACTThe radiation-attenuatedSchistosoma mansonivaccine is highly effective in rodents and primates but has never been tested in humans, primarily for safety reasons. To strengthen its status as a paradigm for a human recombinant antigen vaccine, we have undertaken a small-scale vaccination and challenge experiment in chimpanzees (Pan troglodytes). Immunological, clinical, and parasitological parameters were measured in three animals after multiple vaccinations, together with three controls, during the acute and chronic stages of challenge infection up to chemotherapeutic cure. Vaccination induced a strong in vitro proliferative response and early gamma interferon production, but type 2 cytokines were dominant by the time of challenge. The controls showed little response to challenge infection before the acute stage of the disease, initiated by egg deposition. In contrast, the responses of vaccinated animals were muted throughout the challenge period. Vaccination also induced parasite-specific immunoglobulin M (IgM) and IgG, which reached high levels at the time of challenge, while in control animals levels did not rise markedly before egg deposition. The protective effects of vaccination were manifested as an amelioration of acute disease and overall morbidity, revealed by differences in gamma-glutamyl transferase level, leukocytosis, eosinophilia, and hematocrit. Moreover, vaccinated chimpanzees had a 46% lower level of circulating cathodic antigen and a 38% reduction in fecal egg output, compared to controls, during the chronic phase of infection.
Characterization ofHaemophilus ducreyi cdtA, cdtB, andcdtCMutants in In Vitro and In Vivo Systems
Authors: Lewis David A. , Stevens Marla K. , Latimer Jo L. , Ward Christine K. , Deng Kaiping , Blick Robert , Lumbley Sheryl R. , Ison Catherine A. , Hansen Eric J. 
Published: July 2002

ABSTRACTHaemophilus ducreyiexpresses a soluble cytolethal distending toxin (CDT) that is encoded by thecdtABCgene cluster and can be detected in culture supernatant fluid by its ability to kill HeLa cells. ThecdtA, cdtB, andcdtCgenes ofH. ducreyiwere cloned independently into plasmid vectors, and their encoded proteins expressed singly or in various combinations in anEscherichia colibackground. All three gene products had to be expressed in order forE. coli-derived culture supernatant fluids to demonstrate cytotoxicity for HeLa cells. IsogenicH. ducreyi cdtAandcdtBmutants were constructed and used in combination with the wild-type parent strain and a previously describedH. ducreyi cdtCmutant (M. K. Stevens, J. L. Latimer, S. R. Lumbley, C. K. Ward, L. D. Cope, T. Lagergard, and E. J. Hansen, Infect. Immun. 67:3900–3908, 1999) to determine the relative contributions of the CdtA, CdtB, and CdtC proteins to CDT activity. Expression of CdtA, CdtB, and CdtC appeared necessary forH. ducreyi-derived culture supernatant fluid to exhibit cytotoxicity for HeLa cells. Whole-cell sonicates and periplasmic extracts from thecdtBandcdtCmutants had no effect on HeLa cells, whereas these same fractions from acdtAmutant had a very modest cytotoxic effect on these same human cells. CdtA appeared to be primarily associated with theH. ducreyicell envelope, whereas both CdtB and CdtC were present primarily in the soluble fraction from sonicated cells. Both thecdtAmutant and thecdtBmutant were found to be fully virulent in the temperature-dependent rabbit model for experimental chancroid.
Fas/Fas Ligand System Mediates Epithelial Injury, but Not Pulmonary Host Defenses, in Response to Inhaled Bacteria
Authors: Matute-Bello Gustavo , Frevert Charles W. , Liles W. Conrad , Nakamura Morio , Ruzinski John T. , Ballman Kimberly , Wong Venus A. , Vathanaprida Charie , Martin Thomas R. 
Published: July 2002

ABSTRACTThe Fas/Fas ligand (FasL) system has been implicated in alveolar epithelial cell apoptosis during pulmonary fibrosis and acute respiratory distress syndrome. However, Fas ligation can also lead to cell activation and cytokine production. The goal of this study was to determine the role of the Fas/FasL system in host defenses againstEscherichia coli,Staphylococcus aureus,andStreptococcus pneumoniae. We administered bacteria by aerosolization into the lungs of Fas-deficient (lpr) mice and wild-type (C57BL/6) mice and measured bacterial clearance at 6 and 12 h. One hour prior to euthanasia, the mice received an intraperitoneal injection of human serum albumin (HSA) for alveolar permeability determinations. At all times after bacterial challenges, the lungs of thelprmice contained similar or lower numbers of bacteria than those of the C57BL/6 mice. Alveolar permeability changes, as determined by bronchoalveolar lavage fluid HSA concentrations, were less severe in thelprmice 6 h after the challenges. In response toE. coli, thelprmice had significantly more polymorphonuclear leukocytes (PMN) and macrophage inflammatory protein 2 in the lungs, whereas histopathologic changes were less severe. In contrast, in response to the gram-positive cocci, thelpranimals had similar or lower numbers of PMN. We conclude that the Fas/FasL system contributes to the development of permeability changes and tissue injury during-gram negative bacterial pneumonia. The Fas/FasL system did not have a major role in the clearance of aerosolized bacteria from the lungs at the bacterial doses tested.
In Vivo and In Vitro Studies of Cytosolic Phospholipase A2Expression inHelicobacter pyloriInfection
Authors: Nardone Gerardo , Holicky Eileen L. , Uhl James R. , Sabatino Lina , Staibano Stefania , Rocco Alba , Colantuoni Vittorio , Manzo Barbara A. , Romano Marco , Budillon Gabriele , Cockerill Franklin R. , Miller Laurence J. 
Published: July 2002

ABSTRACTModifications of mucosal phospholipids have been detected in samples from patients withHelicobacter pylori-positive gastritis. These alterations appear secondary to increased phospholipase A2activity (PLA2). The cytosolic form of this enzyme (cPLA2), normally involved in cellular signaling and growth, has been implicated in cancer pathogenesis. The aim of this study was to investigate cPLA2expression and PLA2activity in the gastric mucosae of patients with and withoutH. pyloriinfection. In gastric biopsies from 10H. pylori-positive patients, cPLA2levels, levels of mRNA as determined by reverse transcriptase PCR, levels of protein as determined by immunohistochemistry, and total PLA2activity were higher than in 10H. pylori-negative gastritis patients. To clarify whetherH. pylorihad a direct effect on the cellular expression of cPLA2, we studied cPLA2expression in vitro with different human epithelial cell lines, one from a patient with larynx carcinoma (i.e., HEp-2 cells) and two from patients with gastric adenocarcinoma (i.e., AGS and MKN 28 cells), incubated with differentH. pyloristrains. The levels of cPLA2, mRNA, and protein expression were unchanged in Hep-2 cells independently of cellular adhesion or invasion of the bacteria. Moreover, no change in cPLA2protein expression was observed in AGS or MKN 28 cells treated with wild-typeH. pylori. In conclusion, our study shows increased cPLA2expression and PLA2activity in the gastric mucosae of patients withH. pyloriinfection and no change in epithelial cell lines exposed toH. pylori.
Isolation and Characterization of a
Vibrio vulnificus
Mutant Deficient in Both Extracellular Metalloprotease and Cytolysin
Authors: Fan Jong-Jin , Shao Chung-Ping , Ho Ya-Chi , Yu Chun-Keung , Hor Lien-I 
Published: July 2002

ABSTRACT

We isolated a
Vibrio vulnificus
mutant that was deficient in both metalloprotease and cytolysin by allelic exchange. The virulence of this mutant in mice and its cytotoxicity for HEp-2 cells were comparable to those of the wild-type strain, indicating that neither factor was essential for these properties. The cytolysin, but not the protease, seemed to be important for causing damage in the alimentary tract of the mice.
Neisserial Immunoglobulin A1 Protease Induces Specific T-Cell Responses in Humans
Authors: Tsirpouchtsidis Anastasios , Hurwitz Robert , Brinkmann Volker , Meyer Thomas F. , Haas Gaby 
Published: July 2002

ABSTRACTWe have previously shown that immunoglobulin A1 (IgA1) protease, an exoenzyme of pathogenic neisseriae, can trigger the release of proinflammatory cytokines from human monocytic subpopulations. Here, we demonstrate a dose-dependent T-cell response to recombinant gonococcal IgA1 protease (strain MS11) in healthy human blood donors. This response was delayed in comparison to the immune response against tetanus toxoid. Stimulation with IgA1 protease led to the activation of CD4+and CD8+T cells, as well as CD19+B cells and CD56+NK cells, indicated by de novo expression of CD69. Only CD4+T cells proliferated and stained positive for intracellular gamma interferon (IFN-γ). Both proliferation and IFN-γ production were dependent on antigen presentation via major histocompatibility complex class II. Peripheral blood mononuclear cells stimulated with IgA1 protease produce IFN-γ and tumor necrosis factor alpha but no, or very low amounts of, interleukin-10 (IL-10) or IL-4, indicating a Th1-based proinflammatory immune response. These findings support the significance of IgA1 protease as a virulence determinant of bacterial meningitis and its function as a dominant proinflammatory T-cell antigen.
Variations in the
csgD
Promoter of
Escherichia coli
O157:H7 Associated with Increased Virulence in Mice and Increased Invasion of HEp-2 Cells
Authors: Uhlich Gaylen A. , Keen James E. , Elder Robert O. 
Published: July 2002

ABSTRACT

Promoter alterations in the
csgD
gene of
Escherichia coli
O157:H7 strains ATCC 43894 and ATCC 43895 are associated with variations in curli expression and the ability to bind Congo red dye. Red variants of each strain were more invasive for cultured HEp-2 cells than were white variants. An ATCC 43895 red variant was more virulent than a white variant in a mouse model. However, there were no differences in Shiga toxin production between red and white variants.
Porphyromonas gingivalis
Fimbriae Bind to Cytokeratin of Epithelial Cells
Authors: Sojar Hakimuddin T. , Sharma Ashu , Genco Robert J. 
Published: July 2002

ABSTRACT

The adherence of
Porphyromonas gingivalis
to host cells is likely a prerequisite step in the pathogenesis of
P. gingivalis
-induced periodontal disease.
P. gingivalis
binds to and invades epithelial cells, and fimbriae are shown to be involved in this process. Little is known regarding epithelial receptor(s) involved in binding of
P. gingivalis
fimbriae. Using an overlay assay with purified
P. gingivalis
fimbriae as a probe, two major epithelial cell proteins with masses of 50 and 40 kDa were identified by immunoblotting with fimbria-specific antibodies. Iodinated purified fimbriae also bound to the same two epithelial cell proteins. An affinity chromatography technique was utilized to isolate and purify the epithelial components to which
P. gingivalis
fimbriae bind. Purified fimbriae were coupled to CNBr-activated Sepharose-4B, and the solubilized epithelial cell extract proteins bound to the immobilized fimbriae were isolated from the column. A major 50-kDa component and a minor 40-kDa component were purified and could be digested with trypsin, suggesting that they were proteins. These affinity-eluted 50- and 40-kDa proteins were then subjected to amino-terminal sequencing, and no sequence could be determined, suggesting that these proteins have blocked amino-terminal residues. CNBr digestion of the 50-kDa component resulted in an internal sequence homologous to that of Keratin I molecules. Further evidence that
P. gingivalis
fimbriae bind to cytokeratin molecule(s) comes from studies showing that multicytokeratin rabbit polyclonal antibodies cross-react with the affinity-purified 50-kDa epithelial cell surface component. Also, binding of purified
P. gingivalis
fimbriae to epithelial components can be inhibited in an overlay assay by multicytokeratin rabbit polyclonal antibodies. Furthermore, we showed that biotinylated purified fimbriae bind to purified human epidermal keratin in an overlay assay. These studies suggest that the surface-accessible epithelial cytokeratins may act as receptor(s) for
P. gingivalis
fimbriae. We hypothesize that adherence of
P. gingivalis
fimbriae to cytokeratin may be important for colonization of oral mucous membranes and possibly also for activation of epithelial cells.
Autocrine and Exocrine Regulation of Interleukin-10 Production in THP-1 Cells Stimulated withBorrelia burgdorferiLipoproteins
Authors: Giambartolomei Guillermo H. , Dennis Vida A. , Lasater Barbara L. , Murthy P. K. , Philipp Mario T. 
Published: July 2002

ABSTRACTWe have recently demonstrated that interleukin-10 (IL-10), produced by THP-1 monocytes in response toBorrelia burgdorferilipoproteins, dampens the production of concomitantly elicited inflammatory cytokines. Thus, IL-10 could potentially down-regulate inflammatory and microbicidal effector mechanisms of the innate immune response to aB. burgdorferiinfection, facilitating the establishment of the spirochete. To understand the mechanism(s) implicated in the regulation of the synthesis and release of IL-10 during early infection, we investigated the autocrine effects of IL-6, IL-12, tumor necrosis factor alpha (TNF-α), and IL-10 itself, as well as the exocrine effect of IFN-γ on the production of macrophage-derived IL-10 with lipoprotein as a stimulant. In addition, in view of the differences in the receptor and signal transduction pathways of lipopolysaccharide (LPS) and bacterial lipoproteins, we also investigated the effects described above with LPS as a stimulant. The THP-1 human monocytic cell line and purified recombinant lipidated OspA (L-OspA) were used as the model target cell and stimulant, respectively. TNF-α increased the production of IL-10, as elicited by lipoproteins. The production of IL-10 by THP-1 cells stimulated with L-OspA was autoregulated by a negative feedback mechanism involving the IL-10 receptor (IL-10R). Exogenous IFN-γ significantly inhibited the production of IL-10. Both autocrine (IL-10) and exocrine (IFN-γ) inhibition of IL-10 production resulted in an increase in the production of the proinflammatory cytokines IL-6 and IL-12. The same results were obtained when the stimulant was LPS. The results further illustrate that IL-10 may play a pivotal role in Lyme disease pathogenesis. Moreover, the regulation of its production with lipoprotein as a stimulant is indistinguishable from that observed when LPS acts as a stimulant.
Inhibition of Apoptosis by Gamma Interferon in Cells and Mice Infected withChlamydia muridarum(the Mouse Pneumonitis Strain ofChlamydia trachomatis)
Authors: Perfettini Jean-Luc , Darville Toni , Dautry-Varsat Alice , Rank Roger G. , Ojcius David M. 
Published: July 2002

ABSTRACTThe effect of gamma interferon (IFN-γ) on apoptosis due to infection byChlamydia muridarum(the mouse pneumonitis strain ofChlamydia trachomatis) was studied in epithelial cells in culture and in the genital tracts of mice. IFN-γ concentrations that induce the formation of aberrant, persistent chlamydiae inhibit apoptosis due toC. muridaruminfection. In cells treated with an IFN-γ concentration that leads to the development of a heterogenous population of normal and aberrantChlamydiavacuoles, apoptosis was inhibited preferentially in cells that contained the aberrant vacuoles. The inhibitory effect of IFN-γ appears to be due in part to expression of host cell indoleamine 2,3-dioxygenase activity, since inhibition of apoptosis could be partially reversed through coincubation with exogenous tryptophan. Apoptotic cells were observed in the genital tracts of wild-type mice infected withC. muridarum, and a significantly larger number of apoptotic cells was detected in infected IFN-γ-deficient mice. These results suggest that IFN-γ may contribute to pathogenesis of persistentChlamydiainfections in vivo by preventing apoptosis of infected cells.
Relationship of
Yersinia pseudotuberculosis
O Antigens IA, IIA, and IVB: the IIA Gene Cluster Was Derived from That of IVB
Authors: Pacinelli Elvia , Wang Lei , Reeves Peter R. 
Published: July 2002

ABSTRACT

O antigen is part of the lipopolysaccharide present in the outer membrane of gram-negative bacteria and is highly polymorphic. In this study, we obtained sequences of the O-antigen gene clusters for the
Yersinia pseudotuberculosis
antigens IA, IIA, and IVB. We propose that the IIA gene cluster was derived from the IVB cluster, one of the very few cases in which a parent gene cluster is identified, and that the IA gene cluster could be a hybrid of the IVB and IB gene clusters. All three O antigens contain 6-deoxy
-d-
mannoheptose, and we identified six genes for the biosynthetic pathway for the precursor of this sugar, GDP-6-deoxy
-d-
mannoheptose.
Immunogenicity and Protective Efficacy of Neonatal Vaccination against Bordetella pertussis in a Murine Model: Evidence for Early Control of Pertussis
Authors: Roduit Caroline , Bozzotti Paola , Mielcarek Nathalie , Lambert Paul-Henri , del Giudice Giuseppe , Locht Camille , Siegrist Claire-Anne 
Published: July 2002

ABSTRACTA significant resurgence of early cases of pertussis is being observed in infants too young to have yet completed their three-dose vaccination schedule. In this study, murine models of immunization andBordetella pertussischallenge were adapted to early life. This allowed comparative evaluation of immunogenicity and protective efficacy of immunization initiated in the neonatal period (7-day-old mice) or in infancy (3-week-old mice) with diphtheria-tetanus-whole-cell pertussis (DTPw) and diphtheria-tetanus-acellular pertussis (DTPa) vaccines. Neonatal DTPa vaccination induced strong pertussis-specific antibody and memory responses. Patterns of bacterial clearance were similar in both age groups. In contrast, as observed in human neonates, neonatal DTPw priming did not induce significant antibody responses to pertussis toxin (PT) and filamentous hemagglutinin (FHA) and even interfered with subsequent antibody responses. However, this did not reflect induction of permanent neonatal tolerance, as antigen-specific antibodies could be elicited by subsequent exposure to DTPa. Furthermore, despite these blunted PT and FHA antibody responses, the protective efficacy of DTPw in neonatal mice proved similar to that in infant mice, resulting in complete bacterial clearance at day 8 afterB. pertussischallenge. Thus, neonatal priming with antipertussis vaccines should be considered to reduce the window of vulnerability to pertussis at the time of its greatest severity.
TheSalmonella entericaSerotype Typhimurium Effector Proteins SipA, SopA, SopB, SopD, and SopE2 Act in Concert To Induce Diarrhea in Calves
Authors: Zhang Shuping , Santos Renato L. , Tsolis Renee M. , Stender Silke , Hardt Wolf-Dietrich , Bäumler Andreas J. , Adams L. Garry 
Published: July 2002

ABSTRACTSalmonella entericaserotype Typhimurium requires a functional type III secretion system encoded bySalmonellapathogenicity island 1 (SPI1) to cause diarrhea. We investigated the role of genes encoding secreted target proteins of the SPI1-associated type III secretion system for enteropathogenicity in calves.Salmonellaserotype Typhimurium strains having mutations insptP,avrA,sspH1, orslrPinduced fluid secretion in the bovine ligated ileal loop model at levels similar to that of the wild type. In contrast, mutations insipA,sopA,sopB,sopD, orsopE2significantly reduced fluid accumulation in bovine ligated ileal loops at 8 h postinfection. A strain carrying mutations insipA,sopA,sopB,sopD, andsopE2(sipA sopABDE2mutant) caused the same level of fluid accumulation in bovine ligated ileal loops as a strain carrying a mutation insipB, a SPI1 gene required for the translocation of effector proteins into host cells. A positive correlation was observed between the severity of histopathological lesions detected in the ileal mucosa and the levels of fluid accumulation induced by the different mutants. After oral infection of calves, theSalmonellaserotype TyphimuriumsipAsopABDE2mutant caused only mild diarrhea and was more strongly attenuated than strains having only single mutations. These data demonstrate that SipA, SopA, SopB, SopD, and SopE2 are major virulence factors responsible for diarrhea duringSalmonellaserotype Typhimurium infection of calves.