bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of
Clostridium perfringens
Alpha-Toxin (PLC) and Perfringolysin O (PFO) on Cytotoxicity to Macrophages, on Escape from the Phagosomes of Macrophages, and on Persistence of
C. perfringens
in Host Tissues
Authors: O'Brien David K. , Melville Stephen B. 
Published: August 2004

ABSTRACT

Clostridium perfringens
is the most common cause of clostridial myonecrosis (gas gangrene). Polymorphonuclear cells (PMNs) appear to play only a minor role in preventing the onset of myonecrosis in a mouse animal model of the disease (unpublished results). However, the importance of macrophages in the host defense against
C. perfringens
infections is still unknown. Two membrane-active toxins produced by the anaerobic
C. perfringens
, alpha-toxin (PLC) and perfringolysin O (PFO), are thought to be important in the pathogenesis of gas gangrene and the lack of phagocytic cells at the site of infection. Therefore,
C. perfringens
mutants lacking PFO and PLC were examined for their relative cytotoxic effects on macrophages, their ability to escape the phagosome of macrophages, and their persistence in mouse tissues.
C. perfringens
survival in the presence of mouse peritoneal macrophages was dependent on both PFO and PLC. PFO was shown to be the primary mediator of
C. perfringens
-dependent cytotoxicity to macrophages. Escape of
C. perfringens
cells from phagosomes of macrophage-like J774-33 cells and mouse peritoneal macrophages was mediated by either PFO or PLC, although PFO seemed to play a more important role in escape from the phagosome in peritoneal macrophages. At lethal doses (10
9
) of bacteria only PLC was necessary for the onset of myonecrosis, while at sublethal doses (10
6
) both PFO and PLC were necessary for survival of
C. perfringens
in mouse muscle tissue. These results suggest PFO-mediated cytotoxicity toward macrophages and the ability to escape macrophage phagosomes may be important factors in the ability of
C. perfringens
to survive in host tissues when bacterial numbers are low relative to those of phagocytic cells, e.g., early in an infection.
Gastric Transcription Profile of
Helicobacter pylori
Infection in the Rhesus Macaque
Authors: Huff Jennifer L. , Hansen Lori M. , Solnick Jay V. 
Published: August 2004

ABSTRACT

Infection with
Helicobacter pylori
is usually asymptomatic but sometimes progresses to peptic ulcer disease or gastric adenocarcinoma. The development of disease involves both host and bacterial factors. In order to better understand host factors in pathogenesis, we studied the gastric transcription profile of
H. pylori
infection in the rhesus macaque by using DNA microarrays. Significant changes were found in the expression of genes important for innate immunity, chemokines and cytokines, cell growth and differentiation, apoptosis, structural proteins, and signal transduction and transcription factors. This broad transcription profile demonstrated expected up-regulation of cell structural elements and the host inflammatory and immune response, as well as the novel finding of down-regulation of heat shock proteins. These results provide a unique view of acute
H. pylori
infection in a relevant animal model system and will direct future studies regarding the host response to
H. pylori
infection.
Contribution of the Major Secreted Yops of
Yersinia enterocolitica
O:8 to Pathogenicity in the Mouse Infection Model
Authors: Trülzsch Konrad , Sporleder Thorsten , Igwe Emeka I. , Rüssmann Holger , Heesemann Jürgen 
Published: August 2004

ABSTRACT

Pathogenic yersiniae (
Yersinia pestis
,
Y. pseudotuberculosis
, and
Y. enterocolitica
) harbor a 70-kb virulence plasmid (pYV) that encodes a type III secretion system and a set of at least six effector proteins (YopH, YopO, YopP, YopE, YopM, and YopT) that are injected into the host cell cytoplasm. Yops (
Yersinia
outer proteins) disturb the dynamics of the cytoskeleton, inhibit phagocytosis by macrophages, and downregulate the production of proinflammatory cytokines, which makes it possible for yersiniae to multiply extracellularly in lymphoid tissue.
Y. enterocolitica
serotype O:8 belongs to the highly mouse-pathogenic group of yersiniae in contrast to
Y. enterocolitica
serotype O:9. However, there has been no systematic study of the contribution of Yops to the pathogenicity of
Y. enterocolitica
O:8 in mice. We generated a set of
yop
gene deletion mutants of
Y. enterocolitica
O:8 by using the novel Red cloning procedure. We subsequently analyzed the contribution of
yopH
,
-O
,
-P
,
-E
,
-M
,
-T
, and -
Q
deletions to pathogenicity after oral and intravenous infection of mice. Here we showed for the first time that a Δ
yopT
deletion mutant colonizes mouse tissues to a greater extent than the parental strain. The Δ
yopO
, Δ
yopP
, and Δ
yopE
mutants were only slightly attenuated after oral infection since they were still able to colonize the spleen and liver and cause systemic infection. The Δ
yopO
mutant was lethal for mice, whereas
ΔyopP
and Δ
yopE
mutants were successfully eliminated from the spleen and liver 2 weeks after infection. In contrast the Δ
yopH
, Δ
yopM
, and Δ
yopQ
mutants were highly attenuated and not able to colonize the spleen and liver on any of the days tested. The Δ
yopH
, Δ
yopO
, Δ
yopP
, Δ
yopE
, Δ
yopM
, and Δ
yopQ
mutants had only modest defects in the colonization of the small intestine and Peyer's patches. The Δ
yopE
mutant was eliminated from the small intestine 3 weeks after infection, whereas the Δ
yopH
,
ΔyopP
,
ΔyopM
, and
ΔyopQ
mutants continued to colonize the small intestine at this time.
Activation of Dendritic Cells by Liposomes Prepared from Phosphatidylinositol Mannosides fromMycobacterium bovisBacillus Calmette-Guérin and Adjuvant Activity In Vivo
Authors: Sprott G. Dennis , Dicaire Chantal J. , Gurnani Komal , Sad Subash , Krishnan Lakshmi 
Published: August 2004

ABSTRACTLiposome vesicles could be formed at 65°C from the chloroform-soluble, total polar lipids (TPL) extracted fromMycobacterium bovisbacillus Calmette-Guérin (BCG). Mice immunized with ovalbumin (OVA) entrapped in TPL liposomes produced both anti-OVA antibody and cytotoxic T lymphocyte responses. Murine bone marrow-derived dendritic cells were activated to secrete interleukin-6 (IL-6), IL-12, and tumor necrosis factor upon exposure to antigen-free TPL liposomes. Three phosphoglycolipids and three phospholipids comprising 96% of TPL were identified as phosphatidylinositol dimannoside, palmitoyl-phosphatidylinositol dimannoside, dipalmitoyl-phosphatidylinositol dimannoside, phosphatidylinositol, phosphatidylethanolamine, and cardiolipin. The activation of dendritic cells by liposomes prepared from each purified lipid component of TPL was evaluated in vitro. A basal activity of phosphatidylinositol liposomes to activate proinflammatory cytokine production appeared to be attributable to the tuberculosteric fatty acyl 19:0 chain characteristic of mycobacterial glycerolipids, as similar lipids lacking tuberculosteric chains showed little activity. Phosphatidylinositol dimannoside was identified as the primary lipid that activated dendritic cells to produce amounts of proinflammatory cytokines several times higher than the basal level, indicating the importance of mannose residues. Although the activity of phosphatidylinositol dimannoside was little influenced by palmitoylation of mannose at C-6, a further palmitoylation at inositol C-3 diminished the induction levels of IL-6 and IL-12. Further, OVA entrapped in palmitoyl-phosphatidylinositol dimannoside liposomes was delivered to dendritic cells for major histocompatibility complex class I presentation more effectively than TPL OVA-liposomes. BCG liposomes containing mannose lipids caused up-regulation of costimulatory molecules and CD40. Thus, the inclusion of pure phosphatidylinositol mannosides of BCG in lipid vesicle vaccines represents a simple and efficient option for targeting antigen delivery and providing immune stimulation.
Involvement of the Lectin Pathway of Complement Activation in Antimicrobial Immune Defense during Experimental Septic Peritonitis
Authors: Windbichler Michaela , Echtenacher Bernd , Hehlgans Thomas , Jensenius Jens C. , Schwaeble Wilhelm , Männel Daniela N. 
Published: August 2004

ABSTRACTA critical first line of defense against infection is constituted by the binding of natural antibodies to microbial surfaces, activating the complement system via the classical complement activation pathway. In this function, the classical activation pathway is supported and amplified by two antibody-independent complement activation routes, i.e., the lectin pathway and the alternative pathway. We studied the contribution of the different complement activation pathways in the host defense against experimental polymicrobial peritonitis induced by cecal ligation and puncture by using mice deficient in either C1q or factors B and C2. The C1q-deficient mice lack the classical complement activation pathway. While infection-induced mortality of wild-type mice was 27%, mortality of C1q-deficient mice was increased to 60%. Mice with a deficiency of both factors B and C2 lack complement activation via the classical, the alternative, and the lectin pathways and exhibit a mortality of 92%, indicating a significant contribution of the lectin and alternative pathways of complement activation to survival. For 14 days after infection, mannan-binding lectin (MBL)-dependent activation of C4 was compromised. Serum MBL-A and MBL-C levels were significantly reduced for 1 week, possibly due to consumption. mRNA expression profiles did not lend support for either of the two MBL genes to respond as typical acute-phase genes. Our results demonstrate a long-lasting depletion of MBL-A and MBL-C from serum during microbial infection and underline the importance of both the lectin and the alternative pathways for antimicrobial immune defense.
Population Structure of theBacillus cereusGroup as Determined by Sequence Analysis of Six Housekeeping Genes and theplcRGene
Authors: Ko Kwan Soo , Kim Jong-Wan , Kim Jong-Man , Kim Wonyong , Chung Sang-in , Kim Ik Jung , Kook Yoon-Hoh 
Published: August 2004

ABSTRACTThe population structure of theBacillus cereusgroup (52 strains ofB. anthracis,B. cereus, andB. thuringiensis) was investigated by sequencing seven gene fragments (rpoB,gyrB,pycA,mdh,mbl,mutS, andplcR). Most of the strains were classifiable into two large subgroups in six housekeeping gene trees but not in theplcRtree. In addition, several consistent clusters were identified, which were unrelated to species distinction. Moreover, interrelationships among these clusters were incongruent in each gene tree. The incongruence length difference test and split decomposition analyses also showed incongruences between genes, suggesting horizontal gene transfer. TheplcRgene was observed to have characteristics that differed from those of the other genes in terms of phylogenetic topology and pattern of sequence diversity. Thus, we suggest that the evolutionary history of the PlcR regulon differs from those of the other chromosomal genes and that recombination of theplcRgene may be frequent. The homogeneity ofB. anthracis, which is depicted as an independent lineage in phylogenetic trees, is suggested to be of recent origin or to be due to the narrow taxonomic definition of species.
Comparison of Disseminated and Nondisseminated Strains ofBorrelia burgdorferiSensu Stricto in Mice Naturally Infected by Tick Bite
Authors: Dolan Marc C. , Piesman Joseph , Schneider Bradley S. , Schriefer Martin , Brandt Kevin , Zeidner Nordin S. 
Published: August 2004

ABSTRACTClinical isolates ofBorrelia burgdorferisensu stricto have been categorized into disseminated and nondisseminated groups based on distinct ribosomal spacer restriction fragment length polymorphism genotypes (RSTs). In order to determine whether transmission by tick bite would alter the dissemination dynamics and disease produced by distinct genotypes, disseminated isolates (RST1), nondisseminated isolates (RST3), and a standard laboratory strain (B-31) were established in a murine cycle utilizing infections transmitted by ticks. B-31 spirochetes circulated in the blood of inbred C3H/HeJ mice longer than in the blood of outbred mice. The majority of C3H mice exposed to RST1-infected ticks contained cultivable spirochetes in their blood for up to 17 days; in contrast, mice exposed to RST3 isolates demonstrated a precipitous decline in infection after day 7 postexposure. A quantitative PCR (q-PCR) assay demonstrated that the densities of spirochetes in blood were similar for the RST1 and RST3 isolates, except during the 2nd week postexposure, when the RST1 isolates displayed a markedly higher density in blood. Spirochete load in the heart and bladder of infected mice was measured by q-PCR at 8 weeks postexposure; the numbers of spirochetes in these tissues were similar for mice infected with either disseminated or nondisseminated strains. Similarly, histopathology samples of heart, bladder, and joint tissue obtained at 8 weeks postexposure did not reveal greater pathology in mice infected with the disseminated isolates. We conclude that although the spirochetemia induced by tick-transmitted disseminated isolates was more intense and of longer duration than that induced by nondisseminated isolates, the resultant pathologies produced by these strains were ultimately similar.
Lack of an Association between Antibodies toPlasmodium falciparumGlycosylphosphatidylinositols and Malaria-Associated Placental Changes in Cameroonian Women with Preterm and Full-Term Deliveries
Authors: Suguitan Amorsolo L. , Gowda D. Channe , Fouda Genevieve , Thuita Lucy , Zhou Ainong , Djokam Rosine , Metenou Simon , Leke Rose G. F. , Taylor Diane Wallace 
Published: August 2004

ABSTRACTSequestration ofPlasmodium falciparumparasites within the placenta often leads to an accumulation of macrophages within the intervillous space and increased production of tumor necrosis factor alpha (TNF-α), a cytokine associated with placental pathology and poor pregnancy outcomes.P. falciparumglycosylphosphatidylinositol (GPI) anchors have been shown to be the major parasite component that induces TNF-α production by monocytes and macrophages. Antibodies againstP. falciparumGPI (anti-PfGPI), however, can inhibit the induction of TNF-α and inflammation. Thus, the study was undertaken to determine whether anti-PfGPI antibodies down-regulate inflammatory-type changes in the placentas of women with malaria. Anti-PfGPI immunoglobulin M (IgM) and IgG levels were measured in 380 pregnant women with or without placental malaria, including those who delivered prematurely and at term. Results showed that anti-PfGPI antibody levels increased with gravidity and age and that malaria infection boosted anti-PfGPI antibodies in pregnant women. However, no association was found between anti-PfGPI antibodies and placental TNF-α levels or the presence of acute or chronic placental malaria. Furthermore, anti-PfGPI antibody levels were similar in women with preterm and full-term deliveries and were not associated with an increase in infant birth weight. Thus, these results fail to support a strong role for anti-PfGPI antibodies in the prevention of chronic placental malaria infections and malaria-associated poor birth outcomes.
Trypanosoma cruziInfection Activates Extracellular Signal-Regulated Kinase in Cultured Endothelial and Smooth Muscle Cells
Authors: Mukherjee Shankar , Huang Huan , Petkova Stefka B. , Albanese Chris , Pestell Richard G. , Braunstein Vicki L. , Christ George J. , Wittner Murray , Lisanti Michael P. , Berman Joan W. , Weiss Louis M. , Tanowitz Herbert B. 
Published: August 2004

ABSTRACTTrypanosoma cruziinfection causes cardiomyopathy and vasculopathy. We examined the consequence of this infection for the mitogen-activated protein kinase (MAPK) pathways, which regulate cell proliferation in cultured human umbilical vein endothelial and vascular smooth muscle cells. Infection of these cells resulted in activation of extracellular signal-regulated kinases 1and 2 (ERK1/2) but not c-Jun N-terminal kinase or p38 MAPK. Treatment of these cells with the MAPK kinase inhibitor PD98059 prior to infection blocked the increase in phosphorylated ERK1/2 seen with infection. Heat-killed parasites did not activate ERK1/2, indicating that activation of ERK1/2 was dependent on infection of these cells by live parasites. Furthermore, transfection with dominant-negative Raf(301) or Ras(N17) constructs reduced the infection-associated levels of phospho-ERK1/2, indicating that the activation of ERK1/2 involved the Ras-Raf-ERK pathway. Infection also resulted in an increase in activator protein 1 (AP-1) activity, which was inhibited by transfection with a dominant-negative Raf(301) construct.T. cruzi-infected endothelial cells secreted endothelin-1 and interleukin-1β, which activated ERK1/2 and induced cyclin D1 expression in uninfected smooth muscle cells. These data suggest a possible molecular paradigm for the pathogenesis of the vasculopathy and the cardiovascular remodeling associated withT. cruziinfection.
Monocytes from Patients with Indeterminate and Cardiac Forms of Chagas' Disease Display Distinct Phenotypic and Functional Characteristics Associated with Morbidity
Authors: Souza Paulo E. A. , Rocha Manoel O. C. , Rocha-Vieira Etel , Menezes Cristiane A. S. , Chaves Andréa C. L. , Gollob Kenneth J. , Dutra Walderez O. 
Published: August 2004

ABSTRACTMany studies have demonstrated that monocyte-derived macrophages display critical activities in immunity to parasites. The ability of these cells to process and present antigens, produce cytokines, and provide costimulatory signals demonstrates their pivotal role in initiating immune responses. Although potential modulatory function has been attributed to monocytes from patients with Chagas' disease, a systematic phenotypic and functional analysis of these cells has not been performed. In this work, we analyzed the ex vivo expression of important surface molecules (CD11b and HLA-DR) and immunoregulatory cytokines (interleukin-10 [IL-10], IL-12 and tumor necrosis factor alpha [TNF-α]) in CD14+and CD14−monocytes from Chagas' disease patients with polar clinical forms of the disease: indeterminate or severe cardiac. We also evaluated the influence of in vitro infection withT. cruziin the expression of such molecules. We observed that monocytes from indeterminate-disease patients display lower levels of HLA-DR than those from noninfected individuals both ex vivo and after in vitro infection withT. cruzi.Although ex vivo expression of CD11b was similar among the groups, in vitro infection led to decreased expression of this molecule by monocytes from Chagas' disease patients but not from noninfected individuals. Analysis of the expression of immunoregulatory cytokines showed that while monocytes from indeterminate-disease patients are committed to IL-10 expression, a higher percentage of monocytes from cardiac-disease patients express TNF-α after exposure to live parasites. These results suggest that monocytes from indeterminate-disease patients display modulatory characteristics related to low HLA-DR and high IL-10 expression whereas monocytes from cardiac-disease, patients may be committed to induction of inflammatory responses related to high TNF-α expression.
Induction of Protection against Porcine Cysticercosis by Vaccination with Recombinant Oncosphere Antigens
Authors: Flisser Ana , Gauci Charles G. , Zoli André , Martinez-Ocaña Joel , Garza-Rodriguez Adriana , Dominguez-Alpizar Jose Luis , Maravilla Pablo , Rodriguez-Canul Rossana , Avila Guillermina , Aguilar-Vega Laura , Kyngdon Craig , Geerts Stanny , Lightowlers Marshall W. 
Published: August 2004

ABSTRACT

Two recombinant
Taenia solium
oncosphere antigens, designated TSOL18 and TSOL45-1A, were investigated as vaccines to prevent transmission of the zoonotic disease cysticercosis through pigs. Both antigens were effective in inducing very high levels of protection (up to 100%) in three independent vaccine trials in pigs against experimental challenge infection with
T. solium
eggs, which were undertaken in Mexico and Cameroon. This is the highest level of protection that has been achieved against
T. solium
infection in pigs by vaccination with a defined antigen. TSOL18 and TSOL45-1A provide the basis for development of a highly effective practical vaccine that could assist in the control and, potentially, the eradication of human neurocysticercosis.
A
Salmonella fim
Homologue in
Citrobacter freundii
Mediates Invasion In Vitro and Crossing of the Blood-Brain Barrier in the Rat Pup Model
Authors: Hess Petra , Altenhöfer Artur , Khan A. Salam , Daryab Neda , Kim Kwang Sik , Hacker Jörg , Oelschlaeger Tobias A. 
Published: August 2004

ABSTRACT

From the invasive
Citrobacter freundii
strain 3009, an invasion determinant was cloned, sequenced, and expressed. Sequence analysis of the determinant showed high homology with the
fim
determinant from
Salmonella enterica
serovar Typhimurium. The genes of the invasion determinant directed invasion of recombinant
Escherichia coli
K-12 strains into human epithelial cell lines of the bladder and gut as well as mannose-sensitive yeast agglutination and were termed
fim
Cf
genes. Expression of the Fim
Cf
proteins was shown by
35
S labeling and/or Western blotting. In the infant rat model of experimental hematogenous meningitis,
C. freundii
strain 3009 and the in vitro invasive recombinant
E. coli
K-12 strain harboring the
fim
Cf
determinant reached the cerebrospinal fluid, in contrast to the case for the control strain. The
fim
determinant was also necessary for efficient in vitro invasion by
C. freundii
, because a deletion mutant was strongly reduced in its invasion efficiency. The mutation could be complemented in
trans
by the corresponding genes. Invasion by
C. freundii
could be blocked only by
d
-mannose, GlcNAc, and chitin hydrolysate and not by other carbohydrates tested. In contrast, yeast agglutination was not affected by GlcNAc or chitin hydrolysate. This finding indicated mannose residues to be essential for both yeast agglutination and invasion, whereas GlcNAc (oligomer) residues of host cells are involved exclusively in invasion. These results showed the
fim
determinant of
C. freundii
to be responsible for
d
-mannose- and GlcNAc-dependent in vitro invasion without being assembled into pili and for crossing of the blood-brain barrier in the infant rat model.