Recognition by Dendritic Cells Negatively Regulates Allergic Lung Inflammation through a TLR2/MyD88 Pathway.

is an opportunistic fungal pathogen responsible for a spectrum of clinical manifestations. Dendritic cells recognize pathogen-associated molecular patterns of via two main receptor families, Toll-like receptors (TLRs) and C-type lectin receptors (CLR). Here, the importance of TLR and CLR signaling in the regulation of T-helper cell type 2 (Th2) responses was analyzed using a mouse model based on the transfer of bone marrow-derived dendritic cells (BMDCs) pulsed with conidia. BMDCs were generated from mice deficient in either MyD88 or MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1). Both the MyD88 and MALT1 signaling pathway in BMDCs contributed to the production of inflammatory cytokines induced by conidia. Mice sensitized with MyD88 BMDCs pulsed with conidia showed an exacerbated allergic inflammation, with stronger eosinophil recruitment in the BAL and higher Th2 cytokine production compared with mice sensitized with wild-type or MALT1 BMDCs. This exacerbation was not observed when MyD88 BMDCs were pulsed with , a nonpathogenic mold. A lack of TLR2 signaling recapitulated the exacerbation of the Th2 response observed in the absence of MyD88 signaling, whereas TLR2 agonist dampened the response induced with and conidia. IL-10 production by BMDCs in response to was dependent on the expression of TLR2 and MyD88. IL-10 BMDCs exacerbated, whereas MyD88 BMDCs supplemented with exogenous IL-10 decreased the allergic pulmonary inflammation. These results indicate that TLR2/MyD88-specific recognition of PAMPs from conidia can upregulate IL-10 production and downregulate lung eosinophilia and the development of a Th2 response.