Toll-like receptors (TLRs) are recognition molecules for multiple pathogens, including bacteria, viruses, fungi, and parasites. TLR2 forms heterodimers with TLR1 TLR6, which is the initial step in a cascade of events leading to significant innate immune responses, development adaptive immunity pathogens protection from sequelae related infection these pathogens. This review will discuss current status mediated responses by pathogen-associated molecular patterns (PAMPS) on organisms. We...

Abstract The immunopotentiating activity of neisserial porins, the major outer membrane protein pathogenic Neisseria, is mediated by its ability to stimulate B cells and up-regulate surface expression B7-2. This dependent on MyD88 Toll-like receptor (TLR)2 expression, as demonstrated a lack response from or TLR2 knockout mice porins. Using previously described TLR2-dependent reporter constructs, these results were confirmed shown be due induction NF-κB nuclear translocation. first...

Disease-associated strains of Helicobacter pylori produce a potent toxin that is believed to play key role in peptic ulcer disease man. In vitro the causes severe vacuolar degeneration target cells and has thus been termed VacA (for vacuolating cytotoxin A). Cytotoxic activity associated with > 600-kD protein consisting several copies 95-kD polypeptide undergoes specific proteolytic cleavage after release from bacteria 37- 58-kD fragments. Quick freeze, deep etch electron microscopy...

Abstract Porphyromonas gingivalis is a primary etiological agent of chronic periodontal disease, an infection-driven inflammatory disease that leads to the resorption tooth-supporting alveolar bone. We previously reported TLR2 required for P. gingivalis–induced bone loss in vivo, and our vitro work implicated TNF as key downstream mediator. In this study, we show TNF-deficient (Tnf−/−) mice are resistant following oral infection with gingivalis, thus establish central role experimental...

Neisserial porins are strong immune adjuvants and B cell activators. The effect of neisserial porin PorB on activation-induced death was investigated, as a potential additional mechanism the porin's immunopotentiating ability. interact with target cells to localize intracellularly in mitochondrial compartment without negatively affecting cellular survival. Pretreatment Neisseria meningitidis decreased or abrogated damage induced by apoptotic stimuli. In addition, end stage determinants...

Abstract TLR2 plays a key role in the initiation of cellular innate immune responses by wide range bacterial products. TLRs signaling, including and its coreceptors TLR1 TLR6, is mediated number specific ligands. Although many TLR-mediated cell signaling pathways have been elucidated past few years, molecular mechanisms that lead to activation are still poorly understood. In this study, we investigate interaction PorB from Neisseria meningitidis with describe direct binding protein for first...

Abstract Background Gonorrhea, caused by the bacterium Neisseria gonorrhoeae, is a globally prevalent sexually transmitted infection. The dynamics of gonococcal population biology have been poorly defined due to lack resolution in strain typing methods. Methods In this study, we assess how core genome can be used improve our understanding structure compared with current schemes. Results A total 1668 loci were identified as genome. These organized into multilocus sequence scheme (N...

Abstract Neisserial porins have been shown to act as B cell mitogens and immune adjuvants. PorA PorB are the major outer membrane porin proteins of human pathogen Neisseria meningitidis. We that mechanism immunopotentiating capability involves up-regulation T costimulatory ligand, CD86. Due neisserial porin’s ability activate cells potentiate responses, we hypothesized also employs potent stimulatory function dendritic (DC). examined purified N. meningitidis induce maturation murine splenic...

Gonorrhea is a highly prevalent disease resulting in significant morbidity worldwide, with an estimated 106 cases reported annually. Neisseria gonorrhoeae, the causative agent of gonorrhea, colonizes and infects human genital tract often evades host immune mechanisms until successful antibiotic treatment used. The alarming increase antibiotic-resistant strains N. asymptomatic nature this women lack vaccine directed at crucial virulence determinants have prompted us to perform transcriptome...

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We have attempted to express the Helicobacter pylori vacuolating cytotoxin in Escherichia coli. Although 95-kDa VacA polypeptide was expressed abundantly, it completely lacked any biological activity. In addition, this material failed induce neutralizing antibodies after immunization of rabbits. contrast, highly purified high-molecular-mass from supernatant H. cultures active a HeLa cell assay and effectively induced response Neutralizing sera were shown contain high proportion which...

We have previously shown that purified meningococcal porin PorB associates with mitochondria and prevents apoptosis of B cells, Jurkat cells HeLa (Massari et al., 2000, Proc Natl Acad Sci USA 97: 9070–9075). This work examines if intact meningococci a similar effect as porins. It was first determined live do not induce perturb mitochondrial physiology. latter consideration is important Neisserial porins affect the susceptibility to by preventing depolarization cytochrome c release, events...

ABSTRACT Many bacterial components selectively activate immune and nonhematopoietic target cells via Toll-like receptor (TLR) signaling; modulation of such host responses defines the adjuvant properties these products. For example, outer membrane protein porins from Neisseria , Salmonella Shigella are known TLR2 agonists with established systemic mucosal adjuvanticity. Early work indicated that FomA porin Fusobacterium nucleatum has activity in mice. Using a purified recombinant FomA, we...

Neisseria gonorrhoeae causes the sexually transmitted disease gonorrhea exclusively in humans and uses multiple strategies to infect, including acquisition of host sialic acids that cap mask lipooligosaccharide termini, while restricting complement activation. We hypothesized gonococci selectively target human anti-inflammatory acid-recognizing Siglec receptors on innate immune cells blunt responses pro-inflammatory Siglecs SIGLEC pseudogene polymorphisms represent evolutionary adaptations...

Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen and etiologic agent of blinding trachoma. Intracellular signaling pathways leading to host cell inflammation innate immunity include those mediated by Toll-like receptors (TLRs) nucleotide binding oligomerization domain 1 (Nod1) protein. In epithelial cells, TLR-dependent contributes local immune responses via induction inflammatory mediators. There evidence that TLR3, TLR4, and, particularly, TLR2 are critical...

ABSTRACT The vacuolating cytotoxin of Helicobacter pylori , VacA, enters the cytoplasm target cells and causes vacuolar degeneration by interfering with late stages endocytosis. By using indirect immunofluorescence flow cytometry, we have demonstrated that VacA binds to specific high-affinity cell surface receptors this interaction is necessary for intoxication.

Recent emergence of antimicrobial resistance Neisseria gonorrhoeae worldwide has resulted in limited therapeutic choices for treatment infections caused by this organism. We performed global transcriptomic analysis N. subjects with gonorrhea who attended a Nanjing, China, sexually transmitted infection (STI) clinic, where is high and increasing. found that transcriptional responses to differed genital specimens taken from men women, particularly antibiotic gene expression, which was...

Several microbial pathogens can modulate the host apoptotic response to infection, which may contribute immune evasion. Various studies have reported that infection with sexually transmitted disease pathogen Neisseria gonorrhoeae either inhibit or induce apoptosis. N. initiates at mucosal epithelium, and in women, cells from ectocervix endocervix are among first encountered by this pathogen. In study, we defined antiapoptotic effect of human endocervical epithelial (End/E6E7 cells). We...