title: Neither dectin-2 nor the mannose receptor is required for resistance to Coccidioides immitis in mice.
abstract: 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 B6 mice with targeted mutations in Mrc1 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 proinflammatory cytokines in response to FKS by both elicited macrophages and BMDC. Infected MR knockout (KO) mice produced more IL-10 in their lungs than did B6 mice, and MR KO mice 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 KO was required for stimulation of elicited peritoneal macrophages. Despite that, lung cytokine levels were not significantly different in Dectin-2 KO mice and B6 mice 14 days after infection, except for IL-1β, which was higher in Dectin-2 KO lungs. Although both Dectin-2(-/-) and MR(-/-) 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.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, UC San Diego School of Medicine, San Diego, California, USA.
authors.forename: Suganya
authors.initials: S
authors.lastname: Viriyakosol
authors.forename: Maria Del Pilar
authors.initials: Mdel P
authors.lastname: Jimenez
authors.forename: Sinobu
authors.initials: S
authors.lastname: Saijo
authors.forename: Joshua
authors.initials: J
authors.lastname: Fierer
mesh_terms: D000818:Animals; D003045:Coccidioides / Q000276:immunology*; D003047:Coccidioidomycosis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology*; D008168:Lung / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology*; D011971:Receptors, Immunologic; D058504:Th17 Cells / Q000276:immunology
chemical_list: D053583:Interleukin-1beta; D037181:Lectins, C-Type; C581013:MRC1 protein, mouse; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C445340:dectin-2, mouse; D016753:Interleukin-10