Aspergillus fumigatus Recognition by Dendritic Cells Negatively Regulates Allergic Lung Inflammation Through a TLR2/MyD88 Pathway.

Aspergillus fumigatus Recognition by Dendritic Cells Negatively Regulates Allergic Lung Inflammation Through a TLR2/MyD88 Pathway.

Am J Respir Cell Mol Biol. 2020 Sep 24;:

Authors: Percier P, De Prins S, Tima G, Beyaert R, Grooten J, Romano M, Denis O

Abstract
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 Th2 responses was analyzed using a mouse model based on the transfer of bone marrow-derived dendritic cells (BMDCs) pulsed with A.fum conidia. BMDCs were generated from mice deficient in either MyD88 and MALT1. Both the MyD88 and MALT1 signaling pathway in BMDCs contributed to the production of inflammatory cytokines induced by A.fum conidia. Mice sensitized with MyD88-/- BMDCs pulsed in vitro with A.fum conidia showed an exacerbated allergic inflammation, with stronger eosinophil recruitment in the bronchoalveolar lavage and higher Th2 cytokine production as compared to mice sensitized with WT or MALT1-/- BMDCs. This exacerbation was not observed when MyD88-/- BMDCs were pulsed with Cladosporium sphaerospermum, a non-pathogenic mold. A lack of TLR2 signaling recapitulated the exacerbation of the A.fum Th2 response observed in the absence of MyD88 signaling, whereas TLR2 agonist dampened the response induced with A.fum and C.sph conidia. IL-10 production by BMDCs in response to A.fum was dependent on the expression of TLR2 and MyD88. IL-10-/- BMDCs exacerbated while MyD88-/- BMDCs supplemented with exogenous IL-10 decreased the allergic pulmonary inflammation. These results indicate that TLR2/MyD88-specific recognition of PAMPs from A.fum conidia can upregulate IL-10 production and downregulate lung eosinophilia and the development of a Th2 response.

PMID: 32970964 [PubMed – as supplied by publisher]

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