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Toll-Like Receptor 2 Suppresses Immunity against Candida albicans through Induction of IL-10 and Regulatory T Cells

Department of Medicine,, University Medical Center St. Radboud, Nijmegen, The Netherlands.
The Journal of Immunology (Impact Factor: 5.36). 04/2004; 172(6):3712-8. DOI: 10.4049/jimmunol.172.6.3712
Source: PubMed

ABSTRACT Toll-like receptor (TLR) 2 and TLR4 play a pivotal role in recognition of Candida albicans. We demonstrate that TLR2(-/-) mice are more resistant to disseminated Candida infection, and this is associated with increased chemotaxis and enhanced candidacidal capacity of TLR2(-/-) macrophages. Although production of the proinflammatory cytokines TNF, IL-1alpha, and IL-1beta is normal, IL-10 release is severely impaired in the TLR2(-/-) mice. This is accompanied by a 50% decrease in the CD4+CD25+ regulatory T (Treg) cell population in TLR2(-/-) mice. In vitro studies confirmed that enhanced survival of Treg cells was induced by TLR2 agonists. The deleterious role of Treg cells on the innate immune response during disseminated candidiasis was underscored by the improved resistance to this infection after depletion of Treg cells. In conclusion, C. albicans induces immunosuppression through TLR2-derived signals that mediate increased IL-10 production and survival of Treg cells. This represents a novel mechanism in the pathogenesis of fungal infections.

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Available from: Gosse J Adema, Aug 26, 2015
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    • "We were unable to detect a role for TLR-2 in TNF-␣ production by mast cells in response to C. albicans, a phenomenon previously described in murine peritoneal macrophages derived from TLR-2 knockout mice (Netea et al., 2004). However, we cannot discard that TLR-2 is activated in mast cells in response to C. albicans; it is possible that signaling through this PRR is involved in the production of other cytokines production, such as IL-10 (Netea et al., 2004). A recent study showed that mast cells were able to phagocytose C. albicans and produce ROS (Trevisan et al., 2014). "
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    Immunobiology 05/2015; 220(9). DOI:10.1016/j.imbio.2015.05.005 · 3.18 Impact Factor
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    • "Certain dermatophytes like T. rubrum produce substances e.g., the mannans associated with glycoproteins that diminish the immune response thus prevent complete eradication of the fungus [26]. Some fungi other than dermatophyte genera infecting the skin can induce immune-suppression through toll like receptor 2 (TLR2) mediated IL-10 release, and this leads to generation of CD4 + CD25 + T-regulatory cells with immunosuppressive potential [27]. It is suggested that T. rubrum has the ability to suppress the expression of toll like receptors in keratinocytes and Langerhans cells in dermis and epidermis necessary for stimulation of Th1-type cell response. "
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    • "Mice lacking TLR2 exhibit an intrinsic defect in the number of CD4 + CD25 + Treg subset that maintains peripheral tolerance, but may also dampen the immune response to infection (Netea et al., 2004). Upon intravenous Candida infection, absence of Tregs results in improved fungal clearance 7 days after infection and better survival of TLR2 −/− mice when compared to wild-type mice (Bellocchio et al., 2004a; Netea et al., 2004). By contrast, in an intraperitoneal model of candidiasis, clearance is impaired 1 day afterinfection in the absence of TLR2 (Tessarolli et al., 2010). "
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