Efficient responses to host and bacterial signals during<i>Vibrio cholerae</i>colonization

Rothenbacher, Francesca P.; Zhu, Jun

doi:10.4161/gmic.26944

Cited by 34 publications

(21 citation statements)

References 91 publications

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“…The use of microbial substances as vaccine adjuvants may be counteracted by unwanted immune evasion strategies from the respective microbe. Several immune evasion strategies have been described for Vibrio cholerae , however not the induction of CTLA-2 [ 72 ]. Thus the tolerogenic effects observed by CTLA-2 activity may represent a novel mechanism of immune evasion mediated by CT.…”

Section: Discussionmentioning

confidence: 99%

Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion

et al. 2017

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Immature or semi-mature dendritic cells (DCs) represent tolerogenic maturation stages that can convert naive T cells into Foxp3+ induced regulatory T cells (iTreg). Here we found that murine bone marrow-derived DCs (BM-DCs) treated with cholera toxin (CT) matured by up-regulating MHC-II and costimulatory molecules using either high or low doses of CT (CThi, CTlo) or with cAMP, a known mediator CT signals. However, all three conditions also induced mRNA of both isoforms of the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2α and CTLA-2β). Only DCs matured under CThi conditions secreted IL-1β, IL-6 and IL-23 leading to the instruction of Th17 cell polarization. In contrast, CTlo- or cAMP-DCs resembled semi-mature DCs and enhanced TGF-β-dependent Foxp3+ iTreg conversion. iTreg conversion could be reduced using siRNA blocking of CTLA-2 and reversely, addition of recombinant CTLA-2α increased iTreg conversion in vitro. Injection of CTlo- or cAMP-DCs exerted MOG peptide-specific protective effects in experimental autoimmune encephalomyelitis (EAE) by inducing Foxp3+ Tregs and reducing Th17 responses. Together, we identified CTLA-2 production by DCs as a novel tolerogenic mediator of TGF-β-mediated iTreg induction in vitro and in vivo. The CT-induced and cAMP-mediated up-regulation of CTLA-2 also may point to a novel immune evasion mechanism of Vibrio cholerae.

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Section: Discussionmentioning

confidence: 99%

Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion

et al. 2017

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“…43 For example, GmaR, an anti-repressor in Listeria, undergoes a conformational shift at 37 C and is then degraded; loss of GmaR allows MogR to repress genes involved in flagellar based motility within the mammalian host. 42 The interaction between the function and stability of several proteins in a network allows fine tuning of virulence factor expression, as well as the integration of inputs from several environmental stimuli, 44 permitting a more dynamic response.…”

Section: Introductionmentioning

confidence: 99%

Thermal control of virulence factors in bacteria: A hot topic

2014

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Pathogenic bacteria sense environmental cues, including the local temperature, to control the production of key virulence factors. Thermal regulation can be achieved at the level of DNA, RNA or protein and although many virulence factors are subject to thermal regulation, the exact mechanisms of control are yet to be elucidated in many instances. Understanding how virulence factors are regulated by temperature presents a significant challenge, as gene expression and protein production are often influenced by complex regulatory networks involving multiple transcription factors in bacteria. Here we highlight some recent insights into thermal regulation of virulence in pathogenic bacteria. We focus on bacteria which cause disease in mammalian hosts, which are at a significantly higher temperature than the outside environment. We outline the mechanisms of thermal regulation and how understanding this fundamental aspect of the biology of bacteria has implications for pathogenesis and human health.

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“…As previous studies have demonstrated, members of the Vibrio genus respond to anaerobiosis by promoting virulence gene induction, triggering biofilm dispersal and decreasing capsule production 5 6 7 8 . While some of the pathways regulating these phenotypes are known 5 6 , O 2 -dependent stressosome signalling likely plays key roles in Vibrio species in adapting to changing O 2 levels in the marine environment, and also may control virulence of Vibrio pathogens as they transition to the anaerobic/microaerobic gut environment 5 6 7 8 28 29 30 . Recent work on the stressosome from Moorella thermoacetica found that the stressosome also regulates cyclic di-GMP signalling through phosphorylation of a downstream diguanylate cyclase by the RsbT kinase homologue 31 .…”

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confidence: 99%

An O2-sensing stressosome from a Gram-negative bacterium

et al. 2016

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Bacteria have evolved numerous pathways to sense and respond to changing environmental conditions, including, within Gram-positive bacteria, the stressosome complex that regulates transcription of general stress response genes. However, the signalling molecules recognized by Gram-positive stressosomes have yet to be identified, hindering our understanding of the signal transduction mechanism within the complex. Furthermore, an analogous pathway has yet to be described in Gram-negative bacteria. Here we characterize a putative stressosome from the Gram-negative bacterium Vibrio brasiliensis. The sensor protein RsbR binds haem and exhibits ligand-dependent control of the stressosome complex activity. Oxygen binding to the haem decreases activity, while ferrous RsbR results in increased activity, suggesting that the V. brasiliensis stressosome may be activated when the bacterium enters anaerobic growth conditions. The findings provide a model system for investigating ligand-dependent signalling within stressosome complexes, as well as insights into potential pathways controlled by oxygen-dependent signalling within Vibrio species.

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Efficient responses to host and bacterial signals duringVibrio choleraecolonization

Cited by 34 publications

References 91 publications

Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion

Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion

Thermal control of virulence factors in bacteria: A hot topic

An O2-sensing stressosome from a Gram-negative bacterium

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