Toll-Like Receptor 6 Drives Differentiation of Tolerogenic Dendritic Cells and Contributes to LcrV-Mediated Plague Pathogenesis
- 1 October 2008
- journal article
- research article
- Published by Elsevier BV in Cell Host & Microbe
- Vol. 4 (4), 350-361
- https://doi.org/10.1016/j.chom.2008.09.004
Abstract
Educating dendritic cells (DC) to become tolerogenic DC, which promote regulatory IL-10 immune responses, represents an effective immune evasion strategy for pathogens. Yersinia pestis virulence factor LcrV is reported to induce IL-10 production via interaction with Toll-like receptor (TLR) 2. However, TLR2−/− mice are not protected against subcutaneous plague infection. Using complementary in vitro and in vivo approaches and LcrV as a model, we show that TLR6 associates with TLR2 to induce tolerogenic DC and regulatory type-1 T cells selectively secreting IL-10. In contrast, TLR1 heterodimerizes with TLR2 to promote proinflammatory IL-12p40 cytokine, producing DC and inflammatory T cell differentiation. LcrV specifically hijacks the TLR2/6 pathway to stimulate IL-10 production, which blocks host protective inflammatory responses. These results explain why TLR2 can mediate both pro- and anti-inflammatory responses and identify TLR6 as a distinct receptor driving regulatory IL-10 responses.Keywords
This publication has 41 references indexed in Scilit:
- Selective synergy in anti-inflammatory cytokine production upon cooperated signaling via TLR4 and TLR2 in murine conventional dendritic cellsMolecular Immunology, 2008
- Yersinia pestis caf1Variants and the Limits of Plague Vaccine ProtectionInfection and Immunity, 2008
- Role of TLR1 and TLR6 in the host defense against disseminated candidiasisFEMS Immunology & Medical Microbiology, 2008
- Evaluation of the Role of LcrV-Toll-Like Receptor 2-Mediated Immunomodulation in the Virulence of Yersinia pestisInfection and Immunity, 2007
- Adjuvant-Enhanced Antibody Responses in the Absence of Toll-Like Receptor SignalingScience, 2006
- Virulence factors of Yersinia pestis are overcome by a strong lipopolysaccharide responseNature Immunology, 2006
- Interleukin-10 and Inhibition of Innate Immunity to Yersiniae: Roles of Yops and LcrV (V Antigen)Infection and Immunity, 2003
- Recognition of lipopeptides by Toll-like receptorsInnate Immunity, 2002
- Yersinia V–Antigen Exploits Toll-like Receptor 2 and CD14 for Interleukin 10–mediated ImmunosuppressionThe Journal of Experimental Medicine, 2002
- Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor.The Journal of Experimental Medicine, 1992