bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Complement inMycobacterium aviumPathogenesis: In Vivo and In Vitro Analyses of the Host Response to Infection in the Absence of Complement Component C3
Authors: Bohlson Suzanne S. , Strasser Jennifer A. , Bower Jacquelyn J. , Schorey Jeffrey S. 
Published: July 2002

ABSTRACTWe investigated the importance of the host complement system in the pathogenesis of disease mediated by the intramacrophage pathogenMycobacterium avium. Mycobacteria opsonized with complement are efficiently ingested by macrophages through various complement receptors. Furthermore, unlike other bacteria, mycobacteria can activate both the alternative and classical complement pathways in the absence of specific antibodies. Therefore, to examine the role of complement in the mycobacterial infection process in vivo, mice deficient in complement component C3 were infected withM. avium.Surprisingly, C3-deficient mice infected intravenously withM. aviumdisplayed no difference in bacterial burden or granulomatous response compared to wild-type control mice. C3-sufficient mice and C3-deficient mice were equally susceptible to infection byM. aviumregardless of the genotype at thebcglocus, a locus known to confer susceptibility to infection with intracellular pathogens. In vitro studies using mouse bone marrow-derived macrophages resulted in significantM. aviuminvasion of macrophages in the absence of C3; however, the kinetics of infection were delayed compared to complement-mediated invasion. The data indicate that complement does not play an essential role in mediatingM. aviuminfections in the mouse and suggest either that other invasion mechanisms can compensate for the absence of complement-mediated entry or that complement is not a major mycobacterial opsonin in vivo.
Toxoplasma gondiiInfection of Neurons Induces Neuronal Cytokine and Chemokine Production, but Gamma Interferon- and Tumor Necrosis Factor-Stimulated Neurons Fail To Inhibit the Invasion and Growth ofT. gondii
Authors: Schlüter D. , Deckert M. , Hof H. , Frei K. 
Published: July 2002

ABSTRACTThe intracellular parasiteToxoplasmagondiihas the capacity to persist in the brain within neurons. In this study we demonstrated thatT. gondiiinfected murine cerebellar neurons in vitro and replicated within these cells. Stimulation with gamma interferon (IFN-γ) and/or tumor necrosis factor (TNF) did not enable neurons to inhibit parasite invasion and replication. Cultured neurons constitutively produced interleukin 1 (IL-1), IL-6, macrophage inflammatory protein 1α (MIP-1α), and MIP-1β but not transforming growth factor β1 (TGF-β1), IL-10, and granulocyte-macrophage colony-stimulating factor. Neuronal expression of some cytokines (IL-6, TGF-β1) and chemokines (MIP-1β) was regulated by infection and/or by IFN-γ and TNF.
Induction of Neutralizing Antibodies against Diphtheria Toxin by Priming with Recombinant
Mycobacterium bovis
BCG Expressing CRM
197
, a Mutant Diphtheria Toxin
Authors: Miyaji Eliane N. , Mazzantini Rogerio P. , Dias Waldely O. , Nascimento Ana L. T. O. , Marcovistz Rugimar , Matos Denise S. , Raw Isaias , Winter Nathalie , Gicquel Brigitte , Rappuoli Rino , Leite Luciana C. C. 
Published: July 2002

ABSTRACT

BCG, the attenuated strain of
Mycobacterium bovis
, has been widely used as a vaccine against tuberculosis and is thus an important candidate as a live carrier for multiple antigens. With the aim of developing a recombinant BCG (rBCG) vaccine against diphtheria, pertussis, and tetanus (DPT), we analyzed the potential of CRM
197
, a mutated nontoxic derivative of diphtheria toxin, as the recombinant antigen for a BCG-based vaccine against diphtheria. Expression of CRM
197
in rBCG was achieved using
Escherichia coli
-mycobacterium shuttle vectors under the control of
p
BlaF*, an upregulated β-lactamase promoter from
Mycobacterium fortuitum
. Immunization of mice with rBCG-CRM
197
elicited an anti-diphtheria toxoid antibody response, but the sera of immunized mice were not able to neutralize diphtheria toxin (DTx) activity. On the other hand, a subimmunizing dose of the conventional diphtheria-tetanus vaccine, administered in order to mimic an infection, showed that rBCG-CRM
197
was able to prime the induction of a humoral response within shorter periods. Interestingly, the antibodies produced showed neutralizing activity only when the vaccines had been given as a mixture in combination with rBCG expressing tetanus toxin fragment C (FC), suggesting an adjuvant effect of rBCG-FC on the immune response induced by rBCG-CRM
197
. Isotype analysis of the anti-diphtheria toxoid antibodies induced by the combined vaccines, but not rBCG-CRM
197
alone, showed an immunoglobulin G1-dominant profile, as did the conventional vaccine. Our results show that rBCG expressing CRM
197
can elicit a neutralizing humoral response and encourage further studies on the development of a DPT vaccine with rBCG.
Interleukin-12 Promotes Pathologic Liver Changes and Death in Mice Coinfected withSchistosoma mansoniandToxoplasma gondii
Authors: Araujo Maria Ilma , Bliss Susan K. , Suzuki Yasuhiro , Alcaraz Ana , Denkers Eric Y. , Pearce Edward J. 
Published: July 2002

ABSTRACTWe previously demonstrated that mice concurrently infected withSchistosoma mansoniandToxoplasma gondiiundergo accelerated mortality which is preceded by severe liver damage. Abnormally high levels of serum tumor necrosis factor alpha (TNF-α) in the dually infected mice suggested a role for this and related proinflammatory mediators in the pathologic alterations. In order to evaluate the factors involved in increased inflammatory-mediator production and mortality, interleukin-12−/−(IL-12−/−) mice were coinfected withS. mansoniandT. gondii, and survival and immune responses were monitored. These IL-12−/−mice displayed decreased liver damage and prolonged time to death relative to wild-type animals also coinfected with these parasites. Relative to the response of cells from the coinfected wild-type animals, levels of TNF-α, gamma interferon, and NO produced by splenocytes from coinfected IL-12−/−mice were reduced, and levels of IL-5 and IL-10 were increased, with the net result that the immune response of the dually infected IL-12−/−mice was similar to that of the wild-type mice infected withS. mansonialone. While dually infected wild-type animals succumb in the absence of overt parasitemia, the delayed death in the absence of IL-12 is associated with relatively uncontrolledT. gondiireplication. These data support the view thatS. mansoni-infected mice are acutely sensitive to infection withT. gondiias a result of their increased hepatic sensitivity to high levels of proinflammatory cytokines; IL-12 and TNF-α are implicated in this process.
Implication of the Structure of theHelicobacter pylori cagPathogenicity Island in Induction of Interleukin-8 Secretion
Authors: Audibert C. , Burucoa C. , Janvier B. , Fauchère J. L. 
Published: July 2002

ABSTRACTHelicobacter pylorivirulence is associated with the presence of thecagpathogenicity island (PAI). ThecagPAI is involved in the ability to induce interleukin-8 (IL-8) secretion by human cells, which is implicated in the inflammatory response of the gastric mucosa toH. pyloriinfection. The aim of this study was to determine whether the genetic structure of thecagPAI is conserved and whether it is linked to IL-8 induction ability. Detection of specific markers (cagA, picB, cag13-cag14, virD4, and IS605) by PCR and dot blot hybridization and long-distance PCR determination of the presence of cagI, cagII, and the middle region of thecagPAI were performed on 153 strains isolated from adults suffering from ulcers (n= 79) or gastritis (n= 74). IL-8 induction ability was evaluated by coculture of the strains with HEp-2 cells. Eighty-three strains (54.3%) had an entirecagPAI, 12 strains (7.8%) had thecagPAI split in two, 49 strains (32%) had nocagPAI, and 9 strains exhibited other structural combinations. The presence of an entirecagPAI was statistically correlated with the presence of IS605(P= 0.006) and the ability to induce IL-8 secretion but not with clinical presentation of the infection. The structure of thecagPAI appears to be rather conserved and is related to the proinflammatory power of a strain. The existence of strains inducing IL-8 secretion regardless of thecagPAI structure suggests that this region is not the only requirement for IL-8 secretion.
Evaluation of De-O-Acetylated Meningococcal C Polysaccharide-Tetanus Toxoid Conjugate Vaccine in Infancy: Reactogenicity, Immunogenicity, Immunologic Priming, and Bactericidal Activity against O-Acetylated and De-O-Acetylated Serogroup C Strains
Authors: Richmond Peter , Borrow Ray , Findlow Jamie , Martin Sarah , Thornton Carol , Cartwright Keith , Miller Elizabeth 
Published: July 2002

ABSTRACT

The polysaccharide capsule of serogroup C
Neisseria meningitidis
(MenC) has been integral to vaccine development. Licensed MenC vaccines contain the O-acetylated (OAc+) form of polysaccharide. Some MenC strains have de-O-acetylated (OAc−) polysaccharide, which may affect antibody specificity and functional activity when used in a vaccine. We evaluated an OAc-MenC conjugate-tetanus toxoid conjugate (MCC-TT) vaccine given concomitantly with whole-cell diphtheria-tetanus-pertussis,
Haemophilus influenzae
type b, and oral polio immunization in 83 infants at 2, 3, and 4 months of age. Serum bactericidal activities (SBA) against OAc+ and OAc− MenC strains and OAc+ and OAc− polysaccharide-specific immunoglobulin G (IgG) levels were evaluated. MCC-TT vaccine was well tolerated. All infants produced SBA titers of ≥8 after a single dose at 2 months of age. The SBA geometric mean titer for OAc+ strain C11 increased from 2.7 (95% confidence interval [CI] 2.2 to 3.2) to 320 (95% CI, 237 to 432), 773 (95% CI, 609 to 982), and 1,063 (95% CI, 856 to 1319) after one, two, and three doses of MCC-TT, respectively. OAc− IgG levels were twice as high as OAc+ IgG levels after the primary series of MCC-TT vaccine, and the SBA was significantly higher against the OAc− MenC strain. Antibody responses to booster vaccination with either OAc+ MenC polysaccharide vaccine (MACP) or a fourth dose of MCC-TT at 14 months of age provided evidence of immunologic memory. The acetylation status of the booster vaccine influenced the specificity of the response, with significantly higher OAc− IgG levels and SBA after MCC-TT vaccine compared to MACP vaccine but similar OAc+ antibody levels. MCC-TT vaccine is highly immunogenic and primes for immunologic memory against OAc+ and OAc− MenC strains in infancy.
Differential Gene Expression during Meningeal-Meningococcal Interaction: Evidence for Self-Defense and Early Release of Cytokines and Chemokines
Authors: Wells Damien B. , Tighe Patrick J. , Wooldridge Karl G. , Robinson Karen , Ala' Aldeen Dlawer A. A. 
Published: July 2002

ABSTRACT
Using microarray technology, we studied the early differential expression of 3,528 genes in human meningothelial cells in response to meningococcal challenge. Thirty-two genes were up-regulated, and four were down-regulated. Those up-regulated included the tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-8 (but not IL-1β) genes, suggesting that meningeal cells may be a local and early source of these cytokines. Also, a trend in up-regulation of anti-apoptotic genes and down-regulation of pro-apoptotic genes was observed. This is the first evidence that meningothelial cells may mount cytoprotective responses to pathogenic bacteria.
Role ofHelicobacter pylori cagRegion Genes in Colonization and Gastritis in Two Animal Models
Authors: Eaton Kathryn A. , Kersulyte Dange , Mefford Megan , Danon Stephen J. , Krakowka Steven , Berg Douglas E. 
Published: July 2002

ABSTRACTTheHelicobacter pylorichromosomal region known as the cytotoxin-gene associated pathogenicity island (cagPAI) is associated with severe disease and encodes proteins that are believed to induce interleukin (IL-8) secretion by cultured epithelial cells. The objective of this study was to evaluate the relationship between thecagPAI, induction of IL-8, and induction of neutrophilic gastric inflammation. Germ-free neonatal piglets and conventional C57BL/6 mice were given wild-type orcagdeficient mutant derivatives ofH. pyloristrain 26695 or SS1. Bacterial colonization was determined by plate count, gastritis and neutrophilic inflammation were quantified, and IL-8 induction in AGS cells was determined by enzyme-linked immunosorbent assay. Deletion of the entirecagregion or interruption of thevirB10orvirB11homolog had no effect on bacterial colonization, gastritis, or neutrophilic inflammation. In contrast, these mutations had variable effects on IL-8 induction, depending on theH. pyloristrain. In the piglet-adapated strain 26695, which induced IL-8 secretion by AGS cells, deletion of thecagPAI decreased induction. In the mouse-adapted strain SS1, which did not induce IL-8 secretion, deletion of thecagII region or interruption of any of threecagregion genes increased IL-8 induction. These results indicate that in mice and piglets (i) neither thecagPAI nor the ability to induce IL-8 in vitro is essential for colonization or neutrophilic inflammation and (ii) there is no direct relationship between the presence of thecagPAI, IL-8 induction, and neutrophilic gastritis.
Heat-Inducible Surface Stress Protein (Hsp70) Mediates Sulfatide Recognition of the Respiratory PathogenHaemophilus influenzae
Authors: Hartmann Evamarie , Lingwood Clifford A. , Reidl Joachim 
Published: July 2002

ABSTRACTThe in vitro glycolipid binding specificity of clinical strains of nontypeableHaemophilus influenzaeis altered to include sulfated glycolipids following a brief heat shock. We have constructed, expressed, and purified a recombinant protein ofH. influenzaeHsp70, which showed significant specific binding to sulfated galactolipids in vitro. Furthermore, indirect immunofluorescence demonstrates that Hsp70 proteins are surface exposed inH. influenzaeonly after heat shock and are contained in the outer membrane protein fractions.
Escherichia coliHeat-Labile Enterotoxin B Subunit Is a More Potent Mucosal Adjuvant than Its Closely Related Homologue, the B Subunit of Cholera Toxin
Authors: Millar Douglas G. , Hirst Timothy R. , Snider Denis P. 
Published: July 2002

ABSTRACTAlthough cholera toxin (Ctx) andEscherichia coliheat-labile enterotoxin (Etx) are known to be potent mucosal adjuvants, it remains controversial whether the adjuvanticity of the holotoxins extends to their nontoxic, receptor-binding B subunits. Here, we have systematically evaluated the comparative adjuvant properties of highly purified recombinant EtxB and CtxB. EtxB was found to be a more potent adjuvant than CtxB, stimulating responses to hen egg lysozyme when the two were coadministered to mice intranasally, as assessed by enhanced serum and secretory antibody titers as well as by stimulation of lymphocyte proliferation in spleen and draining lymph nodes. These results indicate that, although structurally very similar, EtxB and CtxB have strikingly different immunostimulatory properties and should not be considered equivalent as prospective vaccine adjuvants.
Helicobacter pyloriLipopolysaccharides Preferentially Induce CXC Chemokine Production in Human Monocytes
Authors: Innocenti M. , Svennerholm A.-M. , Quiding-Järbrink M. 
Published: July 2002

ABSTRACTHelicobacter pyloriinfection can cause duodenal ulcers and may also induce gastric adenocarcinoma. The bacteria colonize the gastric mucosa and areas of gastric metaplasia in the duodenum for decades, resulting in active chronic inflammation in the infected areas. A characteristic feature of the infection is the ongoing recruitment of neutrophils to the infected sites. To evaluate the role ofH. pylorilipopolysaccharides (LPS) in the recruitment of leukocytes to the gastric mucosa, we have examined the cytokine and chemokine production from human monocytes stimulated with LPS isolated from differentH. pyloristrains, as well as from several other gram-negative bacteria. Our results show thatH. pyloriLPS induce a large production of neutrophil-recruiting CXC chemokines (interleukin-8 and growth-related oncogene alpha) from purified human monocytes, to almost the same extent asEscherichia coliLPS. However, and in agreement with previous studies,H. pyloriLPS was much less potent in inducing production of proinflammatory cytokines by purified human monocytes and was also a weak inducer of the CC chemokine RANTES. There was no difference between LPS preparations from differentH. pyloristrains in their ability to induce cytokines and chemokines. The preferential production of CXC chemokines after stimulation withH. pyloriLPS indicates an important contribution of this molecule in maintaining neutrophil recruitment during the infection, irrespective of the infecting strain.
Human Antibodies againstPlasmodium falciparumLiver-Stage Antigen 3 Cross-React withPlasmodium yoeliiPreerythrocytic-Stage Epitopes and Inhibit Sporozoite Invasion In Vitro and In Vivo
Authors: Brahimi Karima , Badell Edgar , Sauzet Jean-Pierre , BenMohamed Lbachir , Daubersies Pierre , Guérin-Marchand Claudine , Snounou George , Druilhe Pierre 
Published: July 2002

ABSTRACTThePlasmodium falciparumliver-stage antigen 3 (LSA3), a recently identified preerythrocytic antigen, induces protection against malaria in chimpanzees. Using antibodies from individuals with hyperimmunity to malaria affinity purified on recombinant or synthetic polypeptides of LSA3, we identified four non-cross-reactive B-cell epitopes inPlasmodium yoeliipreerythrocytic stages. On sporozoites theP. yoeliiprotein detected has a molecular mass similar to that of LSA3. T-cell epitopes cross-reacting withP. yoeliiwere also demonstrated using peripheral blood lymphocytes from LSA3-immunized chimpanzees. In contrast, no cross-reactive epitopes were found inPlasmodium berghei. LSA3-specific human antibodies exerted up to 100% inhibition of in vitro invasion ofP. yoeliisporozoites into mouse hepatocytes. This strong in vitro activity was reproduced in vivo by passive transfer of LSA3 antibodies. These results indicate that the homologous epitopes may be biologically functional and suggest thatP. yoeliicould be used as a model to assess the antisporozoite activity of anti-LSA3 antibodies.
Structural and Genetic Analyses of O Polysaccharide from
Actinobacillus actinomycetemcomitans
Serotype f
Authors: Kaplan Jeffrey B. , Perry Malcolm B. , MacLean Leann L. , Furgang David , Wilson Mark E. , Fine Daniel H. 
Published: July 2002

ABSTRACT

The oral bacterium
Actinobacillus actinomycetemcomitans
is implicated as a causative agent of localized juvenile periodontitis (LJP).
A. actinomycetemcomitans
is classified into five serotypes (a to e) corresponding to five structurally and antigenically distinct O polysaccharide (O-PS) components of their respective lipopolysaccharide molecules. Serotype b has been reported to be the dominant serotype isolated from LJP patients. We determined the lipopolysaccharide O-PS structure from
A. actinomycetemcomitans
CU1000, a strain isolated from a 13-year-old African-American female with LJP which had previously been classified as serotype b. The O-PS of strain CU1000 consisted of a trisaccharide repeating unit composed of
l
-rhamnose and 2-acetamido-2-deoxy-
d
-galactose (molar ratio, 2:1) with the structure →2)-α-
l
-Rha
p
-(1–3)-2-
O
-(β-
d
-Gal
p
NAc)-α-
l
-Rha
p
-(1→. O-PS from strain CU1000 was structurally and antigenically distinct from the O-PS molecules of the five known
A. actinomycetemcomitans
serotypes. Strain CU1000 was mutagenized with transposon IS
903
φ
kan
, and three mutants that were deficient in O-PS synthesis were isolated. All three transposon insertions mapped to a single 1-kb region on the chromosome. The DNA sequence of a 13.1-kb region surrounding these transposon insertions contained a cluster of 14 open reading frames that was homologous to gene clusters responsible for the synthesis of
A. actinomycetemcomitans
serotype b, c, and e O-PS antigens. The CU1000 gene cluster contained two genes that were not present in serotype-specific O-PS antigen clusters of the other five known
A. actinomycetemcomitans
serotypes. These data indicate that strain CU1000 should be assigned to a new
A. actinomycetemcomitans
serotype, designated serotype f. A PCR assay using serotype-specific PCR primers showed that 3 out of 20 LJP patients surveyed (15%) harbored
A. actinomycetemcomitans
strains carrying the serotype f gene cluster. The finding of an
A. actinomycetemcomitans
serotype showing serological cross-reactivity with anti-serotype b-specific antiserum suggests that a reevaluation of strains previously classified as serotype b may be warranted.
Cytokine Responses to Group B Streptococci Induce Nitric Oxide Production in Respiratory Epithelial Cells
Authors: Goodrum Kenneth J. , Poulson-Dunlap Jane 
Published: July 2002

ABSTRACT

Streptococcus agalactiae
(group B streptococcus [GBS]) is a leading cause of neonatal pneumonia, sepsis, and meningitis. Early-onset GBS pneumonia is characterized by marked pulmonary epithelial and endothelial cell injury. Innate proinflammatory responses to GBS infection that may contribute to the respiratory pathology include the synthesis and release of cytokines, prostaglandins, and nitric oxide (NO). The hypothesis that NO is directly induced in lung epithelial cells by invading GBS or indirectly induced by cytokines released by GBS-infected mononuclear cells was tested. A549 transformed human respiratory epithelial cells were directly cultured with GBS, cocultured with GBS-infected human mononuclear cells or purified macrophages, or exposed to conditioned culture medium from human mononuclear cells infected by GBS. The culture medium of A549 cultures was assayed for NO secretion, and the cell lysates were tested for presence of inducible nitric oxide synthase (iNOS) mRNA by reverse transcriptase PCR (RT-PCR). GBS-treated A549 cells neither secreted detectable NO nor expressed iNOS mRNA. GBS interaction with human mononuclear cells, however, stimulated release of soluble factors that readily induced iNOS mRNA expression and NO secretion by A549 cells. Inflammatory mediator-induced nitric oxide (NO) production by alveolar epithelium may exceed that of other lung cell types such as macrophages, and induction during GBS infection may play a significant role in pulmonary defense or free-radical-mediated lung injury.