Signaling via the MyD88 Adaptor Protein in B Cells Suppresses Protective Immunity during Salmonella typhimurium Infection

Neves, Patrícia; Lampropoulou, Vicky; Calderón–Gómez, Elisabeth; Roch, Toralf; Stervbo, Ulrik; Shen, Ping; Kühl, Anja A.; Loddenkemper, Christoph; Haury, Matthias; Nedospasov, Sergei A.; Kaufmann, Stefan H. E.; Steinhoff, Ulrich; Calado, Dinis Pedro; Fillatreau, Simon

doi:10.1016/j.immuni.2010.10.016

Cited by 265 publications

(290 citation statements)

References 59 publications

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“…It is tempting to speculate that MZB may prime CD4 T cells with a regulatory phenotype during the very early stages of infection, which then contribute to suppress protective Th1 responses. A recent study has shown that signaling via MyD88 in B cells suppresses NK cells and T cell responses in Salmonella typhimurium-infected mice (56). In this study, IL-10 was an essential mediator of the B cell inhibitory effects on NK and T cells, and MyD88 was crucial for mediating these effects.…”

Section: Discussionmentioning

confidence: 60%

Marginal Zone B Cells Regulate Antigen-Specific T Cell Responses during Infection

Bankoti

Gupta

Levchenko

et al. 2012

The Journal of Immunology

111

108

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Marginal zone B cells (MZB) participate in the early immune response to several pathogens. In this study, we show that in μMT mice infected with Leishmania donovani, CD8 T cells displayed a greater cytotoxic potential and generated more effector memory cells compared with infected wild type mice. The frequency of parasite-specific, IFN-γ+ CD4 T cells was also increased in μMT mice. B cells were able to capture parasites, which was associated with upregulation of surface IgM and MyD88-dependent IL-10 production. Moreover, MZB presented parasite Ags to CD4 T cells in vitro. Depletion of MZB also enhanced T cell responses and led to a decrease in the parasite burden but did not alter the generation of effector memory T cells. Thus, MZB appear to suppress protective T cell responses during the early stages of L. donovani infection.

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Section: Discussionmentioning

confidence: 60%

Marginal Zone B Cells Regulate Antigen-Specific T Cell Responses during Infection

Bankoti

Gupta

Levchenko

et al. 2012

The Journal of Immunology

111

108

View full text Add to dashboard Cite

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“…Notably, TLRinduced B cell-derived IL-10 production interferes with Ag presentation and T cell activation in a Salmonella infection model (54). Well in line with these findings T cell hyporesponsiveness was recently described in a murine model for chronically persistent S. aureus infection (71), although the exact mechanism promoting T cell anergy remained obscure.…”

Section: Discussionmentioning

confidence: 61%

“…Recently, IL-10-secreting B cells have been identified as important negative regulators in immunity to infection (54). Intrigued by these reports we wanted to know whether SpA-mediated B cell activation could selectively trigger the expansion of this regulatory B cell subset.…”

Section: Cooperation Of Pdc and B Cells Supports Il-10 Productionmentioning

confidence: 99%

Pathogen-Triggered Activation of Plasmacytoid Dendritic Cells Induces IL-10–Producing B Cells in Response to Staphylococcus aureus

Parčina

Miranda-García

Durlanik

et al. 2013

The Journal of Immunology

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Induction of polyclonal B cell activation is a phenomenon observed in many types of infection, but its immunological relevance is unclear. In this study we show that staphylococcal protein A induces T cell–independent human B cell proliferation by enabling uptake of TLR-stimulating nucleic acids via the VH3+ BCR. We further demonstrate that Staphylococcus aureus strains with high surface protein A expression concomitantly trigger activation of human plasmacytoid dendritic cells (pDC). Sensitivity to chloroquine, cathepsin B inhibition, and a G-rich inhibitory oligodeoxynucleotide supports the involvement of TLR9 in this context. We then identify pDC as essential cellular mediators of B cell proliferation and Ig production in response to surface protein A–bearing S. aureus. The in vivo relevancy of these findings is confirmed in a human PBMC Nod/scidPrkdc/γc−/− mouse model. Finally, we demonstrate that co-operation of pDC and B cells enhances B cell–derived IL-10 production, a cytokine associated with immunosuppression and induction of IgG4, an isotype frequently dominating the IgG response to S. aureus. IL-10 release is partially dependent on TLR2-active lipoproteins, a hallmark of the Staphylococcus species. Collectively, our data suggest that S. aureus exploits pDC and TLR to establish B cell–mediated immune tolerance.

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“…mTORC1 is a protein complex that is involved in metabolism and autophagy regulation, and the latter is an important process that enables intracellular bacterial control; therefore, through Akt activation and IL-10 production, Salmonella might regulate autophagy to avoid control by the host. It has been reported that B cells produce IL-10 in response to Salmonella infection [57]. Thus, it is likely that through autocrine mechanisms, IL-10 also contributes to bacterial survival by blocking xenophagy.…”

Section: Discussionmentioning

confidence: 99%

SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells

et al. 2018

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B cells are a target of Salmonella infection, allowing bacteria survival without inducing pyroptosis. This event is due to downregulation of Nlrc4 expression and lack of inflammasome complex activation, which impairs the secretion of IL-1β. YAP phosphorylation is required for downregulation of Nlrc4 in B cells during Salmonella infection; however, the microorganism’s mechanisms underlying the inhibition of the NLRC4 inflammasome in B cells are not fully understood. Our findings demonstrate that the Salmonella effector SopB triggers a signaling cascade involving PI3K, PDK1 and mTORC2 that activates Akt with consequent phosphorylation of YAP. When we deleted sopB in Salmonella, infected B cells that lack Rictor, or inhibited the signaling cascade using a pharmacological approach, we were able to restore the function of the NLRC4 inflammasome in B cells and the ability to control the infection. Furthermore, B cells from infected mice exhibited activation of Akt and YAP phosphorylation, suggesting that Salmonella also triggers this pathway in vivo. In summary, our data demonstrate that the Salmonella effector inositide phosphate phosphatase SopB triggers the PI3K-Akt-YAP pathway to inhibit the NLRC4 inflammasome in B cells. This study provides further evidence that Salmonella triggers cellular mechanisms in B lymphocytes to manipulate the host environment by turning it into a survival niche to establish a successful infection.

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Signaling via the MyD88 Adaptor Protein in B Cells Suppresses Protective Immunity during Salmonella typhimurium Infection

Cited by 265 publications

References 59 publications

Marginal Zone B Cells Regulate Antigen-Specific T Cell Responses during Infection

Marginal Zone B Cells Regulate Antigen-Specific T Cell Responses during Infection

Pathogen-Triggered Activation of Plasmacytoid Dendritic Cells Induces IL-10–Producing B Cells in Response to Staphylococcus aureus

SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells

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