Neither Dectin-2 nor the Mannose Receptor Is Required for Resistance to Coccidioides immitis in Mice

We investigated the roles of the mannose receptor (MR) and Dectin-2 in resistance to pulmonary coccidioidomycosis in C57BL/6 (B6) mice and in the interaction of myeloid cells with spherules, using B6mice with targeted mutations inMrc1 and Clec4n. Spherules are the tissue form of Coccidioides, and we determined that the MR on bone marrow-derived dendritic cells (BMDC) was important for recognition of spherules (formalin-killed spherules [FKS]) and for secretion of interleukin 10 (IL-10) and pro-inflammatory cytokines in response to FKS by both elicited macrophages and BMDC. InfectedMR knockout (KO)mice pro-ducedmore IL-10 in their lungs than did B6mice, andMRKOmice also made more protective Th-17 cytokines. In contrast to the MR, Dectin-2 was not required for recognition of FKS by BMDC or for the production of cytokines by BMDC in response to FKS. However, Dectin-2 KOwas required for stimulation of elicited peritoneal macrophages. Despite that, lung cytokine levels were not significantly different in Dectin-2 KOmice and B6mice 14 days after infection, except for IL-1, which was higher in Dectin-2 KO lungs. Although both Dectin-2/ andMR/myeloid cells had reduced proinflammatory cytokine responses to FKS in vitro, neither MR nor Dectin-2 deficiency reduced the resistance of B6 mice to pulmonary coccidioidomycosis. Coccidioidomycosis is a fungal infection endemic to the West-ern Hemisphere that is caused by either of two closely related species, Coccidioides immitis or C. posadasii. Both are dimorphic fungi that grow as spore-forming molds in dry, alkaline desert soil and cause infections in vertebrates after the spores are inhaled. I