TLR-2 Signaling Promotes IL-17A Production in CD4+CD25+Foxp3+ Regulatory Cells during Oropharyngeal Candidiasis

Pathogens
Natarajan BhaskaranPushpa Pandiyan

Abstract

Recent studies show that CD4+CD25+Foxp3+ regulatory cells (Tregs) produce effector cytokines under inflammatory conditions. However, the direct role of microbial agents that serve as toll-like receptor (TLR) ligands in the induction of effector cytokines in Tregs is less clear. Here we show that CD4+Foxp3+Tregs produce the effector cytokine IL-17A during oropharyngeal candidiasis (OPC) and inflammatory bowel disease in a TLR-2/Myd88 signaling dependent manner. TLR-2 ligands promote proliferation in Tregs in the presence and absence of TCR signals and inflammatory cytokines in vitro. The proliferation is directly dependent on TLR-2 expression in Tregs. Consistent with this, Tlr2-/- mice harbor fewer thymically derived Tregs and peripheral Tregs under homeostatic conditions in vivo. However, under Th17 inducing conditions, IL-6 and TLR-2 signaling both in Tregs as well as antigen presenting cells (APC) are critical for maximal ROR-γt and IL-17A up-regulation in Foxp3+ Tregs. The minimal and transient loss of Foxp3 expression and suppressive properties are due to the presence of IL-6 in the milieu, but not the direct effect of TLR-2 signaling in Tregs. Taken together, our data reveal that TLR-2 signaling promotes not only prolifer...Continue Reading

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Citations

Oct 7, 2015·Frontiers in Immunology·Lea-Maxie Haag, Britta Siegmund
Jul 6, 2016·Frontiers in Immunology·Pushpa PandiyanRafick P Sekaly
Nov 17, 2016·European Journal of Pharmacology·Mehdi TaghaviSeyyed Shamsadin Athari
Nov 3, 2017·Immune Network·Min Kyung JungEui-Cheol Shin
Sep 11, 2018·Frontiers in Microbiology·Natarajan BhaskaranPushpa Pandiyan
Mar 25, 2019·Frontiers in Immunology·Pushpa PandiyanJochen Huehn
May 11, 2021·Frontiers in Oncology·Natarajan BhaskaranPushpa Pandiyan
Sep 5, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lucie Bernard-RaichonGeanncarlo Lugo-Villarino

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Methods Mentioned

BETA
flow cytometry
PCR

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Prism
GraphPad
Excel

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