Aspergillus fumigatus is an opportunistic fungal pathogen responsible for a spectrum of clinical manifestations. Dendritic cells recognize pathogen-associated molecular patterns of Aspergillus 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 A. fumigatus 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 A. fumigatus conidia. Mice sensitized with MyD88^−/− BMDCs pulsed in vitro with A. fumigatus 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 Cladosporium sphaerospermum, a nonpathogenic mold. A lack of TLR2 signaling recapitulated the exacerbation of the A. fumigatus Th2 response observed in the absence of MyD88 signaling, whereas TLR2 agonist dampened the response induced with A. fumigatus and C. sphaerospermum conidia. IL-10 production by BMDCs in response to A. fumigatus 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 A. fumigatus conidia can upregulate IL-10 production and downregulate lung eosinophilia and the development of a Th2 response.

烟曲霉是负责多种临床表现的机会性真菌病原体。树突状细胞通过两个主要的受体家族，即Toll样受体（TLR）和C型凝集素受体（CLR）识别曲霉的病原体相关分子模式。在此，使用小鼠模型，基于以烟曲霉分生孢子脉冲的骨髓源性树突状细胞（BMDC）的转移，使用小鼠模型分析了TLR和CLR信号在调节2型T辅助细胞应答中的重要性。BMDC由缺乏MyD88或MALT1（黏膜相关淋巴组织淋巴瘤易位蛋白1）的小鼠产生。BMDCs中的MyD88和MALT1信号通路均促成由DPS诱导的炎性细胞因子的产生烟曲霉分生孢子。与用野生型或MALT1 ^-/- BMDC致敏的小鼠相比，在体外用烟曲霉分生孢子脉冲的MyD88 ^-/- BMDC致敏的小鼠表现出加剧的过敏性炎症，BAL中嗜酸性粒细胞募集更强，Th2细胞因子产生更高。当MyD88 ^-/- BMDC与非致病性霉菌Cladosporium sphaerospermum一起脉冲时，未观察到这种恶化。缺少TLR2信号传导可以重现在没有MyD88信号传导的情况下观察到的烟曲霉Th2反应的加剧，而TLR2激动剂抑制了由烟曲霉和烟曲霉诱导的反应。C. spererospermum分生孢子。BMDC响应烟曲霉产生IL-10的过程取决于TLR2和MyD88的表达。IL-10 ^-/- BMDC加剧，而MyD88 ^-/- BMDC补充外源性IL-10减少了过敏性肺部炎症。这些结果表明，来自烟曲霉分生孢子的PAMP的TLR2 / MyD88特异性识别可以上调IL-10的产生并下调肺嗜酸性粒细胞和Th2反应的发展。