Neisseria gonorrhoeae selectively suppresses the development of Th1 and Th2 cells, and enhances Th17 cell responses, through TGF-β-dependent mechanisms

Liu, Yingru; Islam, Epshita A.; Jarvis, Gary A.; Gray-Owen, Scott D.; Russell, Michael W.

doi:10.1038/mi.2012.12

Cited by 84 publications

(88 citation statements)

References 49 publications

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“…Another pressure may stem from the human adaptive immune system. Opa ϩ Gc proteins prevent maturation and activation of CD4 ϩ T cells and block Th1-and Th2-mediated immunity (65,66). Opa ϩ Gc engagement of CEACAM1 also leads to B cell death (67).…”

Section: Discussionmentioning

confidence: 99%

Constitutively Opa-Expressing and Opa-Deficient Neisseria gonorrhoeae Strains Differentially Stimulate and Survive Exposure to Human Neutrophils

2013

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The Neisseria gonorrhoeae (the gonococcus [Gc]) opacity-associated (Opa) proteins mediate bacterial binding and internalization by human epithelial cells and neutrophils (polymorphonuclear leukocytes [PMNs]). Investigating the contribution of Opa proteins to gonococcal pathogenesis is complicated by high-frequency phase variation of the opa genes. We therefore engineered a derivative of Gc strain FA1090 in which all opa genes were deleted in frame, termed Opaless. Opaless Gc remained uniformly Opa negative (Opa ؊ ), whereas cultures of predominantly Opa ؊ parental Gc and an intermediate lacking the "translucent" subset of opa genes (⌬opaBEGK) stochastically gave rise to Opa-positive (Opa ؉ ) bacterial colonies. Loss of Opa expression did not affect Gc growth. Opaless Gc survived exposure to primary human PMNs and suppressed the PMN oxidative burst akin to parental, Opa ؊ bacteria. Notably, unopsonized Opaless Gc was internalized by adherent, chemokine-primed, primary human PMNs, by an actin-dependent process. When a non-phase-variable, in-frame allele of FA1090 opaD was reintroduced into Opaless Gc, the bacteria induced the PMN oxidative burst, and OpaD ؉ Gc survived less well after exposure to PMNs compared to Opa ؊ bacteria. These derivatives provide a robust system for assessing the role of Opa proteins in Gc biology.

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Section: Discussionmentioning

confidence: 99%

Constitutively Opa-Expressing and Opa-Deficient Neisseria gonorrhoeae Strains Differentially Stimulate and Survive Exposure to Human Neutrophils

2013

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“…Etanercept (a TNF-α soluble receptor, CPGJ-pharm, China, 25 μg/ml), DB-1 (a mouse anti-rat IFN-γ monoclonal antibody, IgG1, 20 μg/ml) and α-IL-17 antibody (a rabbit anti-rat IL-17 antibody, IgG, Santa Cruz, 20 μg/ml) were administrated to T cell conditioned medium accordingly [25][26][27]. FLS were seeded in 6-well plates at a density of 10 5 /well and incubated with PPT medium or control medium for 24 h with or without the above blocker accordingly, and the isotype-matched IgG control were used as controls.…”

Section: Cytokine Blocker Treatmentmentioning

confidence: 99%

Pristane primed rat T cells enhance TLR3 expression of fibroblast-like synoviocytes via TNF-α initiated p38 MAPK and NF-κB pathways

Zhu

Jiang

et al. 2015

Clinical Immunology

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“…In general, gonococcal infection is characterized as a localized and mild disease, and gonococcal infection rarely induces protective immunity against future infection, as evidenced by repetitive infections of individuals with the same strain (20,21). We recently demonstrated that immunosuppression, or immune tolerance, elicited by gonococci was associated with the selective inhibition of Th1 and Th2 cells through the induction of TGF-b along with the enhancement of Th17 cell development in response to TLR4 signaling by LOS (22).…”

mentioning

confidence: 99%

Induction of Endotoxin Tolerance by Pathogenic Neisseria Is Correlated with the Inflammatory Potential of Lipooligosaccharides and Regulated by MicroRNA-146a

John

Jarvis

2014

The Journal of Immunology

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In this article, we report that retreatment of human monocytic THP-1 cells and primary monocytes with pathogenic Neisseria or with purified lipooligosaccharides (LOS) after previous exposure to LOS induced immune tolerance, as evidenced by reduced TNF-α and IL-1β cytokine expression. LOS that we have previously shown to vary in their potential to activate TLR4 signaling, which was correlated with differences in levels of lipid A phosphorylation, had similarly variable ability to induce tolerance. Efficacy for induction of tolerance was proportional to the level of lipid A phosphorylation, as LOS from meningococcal strain 89I with the highest degree of phosphorylation was the most tolerogenic following retreatment with LOS or whole bacteria, compared with LOS from gonococcal strains 1291 and GC56 with reduced levels of phosphorylation. Hydrogen fluoride treatment of 89I LOS to remove phosphates rendered the LOS nontolerogenic. Tolerance induced by the more highly inflammatory meningococcal LOS was correlated with significantly greater downregulation of p38 activation, greater induction of the expression of A20 and of microRNA-146a, and greater reductions in IL-1R–associated kinase 1 and TRAF6 levels following LOS retreatment of cells. The role of miR-146a in regulation of induction of TNF-α was confirmed by transfecting cells with an inhibitor and a mimic of miR-146a. Our results provide a mechanistic framework for understanding the variable pathophysiology of meningococcal and gonococcal infections given that after an initial exposure, greater upregulation of microRNA-146a by more highly inflammatory LOS conversely leads to the suppression of immune responses, which would be expected to facilitate bacterial survival and dissemination.

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Neisseria gonorrhoeae selectively suppresses the development of Th1 and Th2 cells, and enhances Th17 cell responses, through TGF-β-dependent mechanisms

Cited by 84 publications

References 49 publications

Constitutively Opa-Expressing and Opa-Deficient Neisseria gonorrhoeae Strains Differentially Stimulate and Survive Exposure to Human Neutrophils

Constitutively Opa-Expressing and Opa-Deficient Neisseria gonorrhoeae Strains Differentially Stimulate and Survive Exposure to Human Neutrophils

Pristane primed rat T cells enhance TLR3 expression of fibroblast-like synoviocytes via TNF-α initiated p38 MAPK and NF-κB pathways

Induction of Endotoxin Tolerance by Pathogenic Neisseria Is Correlated with the Inflammatory Potential of Lipooligosaccharides and Regulated by MicroRNA-146a

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