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00925njm 22002777a 4500 dc Iborra, Salvador author Martinez-Lopez, Maria author Cueto, Francisco J. author Conde-Garrosa, Ruth author del Fresno, Carlos author Izquierdo-Fernandez, Helena Maria author Abram, Clare L author Mori, Daiki author Campos-Martín, Yolanda author Reguera, Rosa María author Kemp, Benjamin author Yamasaki, Sho author Robinson, Matthew J author Soto, Manuel author Lowell, Clifford A author Sancho, David author 2016-10 C-type lectin receptors sense a diversity of endogenous and exogenous ligands that may trigger differential responses. Here, we have found that human and mouse Mincle bind to a ligand released by Leishmania, a eukaryote parasite that evades an effective immune response. Mincle-deficient mice had milder dermal pathology and a tenth of the parasite burden compared to wild-type mice after Leishmania major intradermal ear infection. Mincle deficiency enhanced adaptive immunity against the parasite, correlating with increased activation, migration, and priming by Mincle-deficient dendritic cells (DCs). Leishmania triggered a Mincle-dependent inhibitory axis characterized by SHP1 coupling to the FcRγ chain. Selective loss of SHP1 in CD11c+ cells phenocopies enhanced adaptive immunity to Leishmania. In conclusion, Leishmania shifts Mincle to an inhibitory ITAM (ITAMi) configuration that impairs DC activation. Thus, ITAMi can be exploited for immune evasion by a pathogen and may represent a paradigm for ITAM-coupled receptors sensing self and non-self. Immunity. 2016; 45(4):788-801 1074-7613 http://hdl.handle.net/20.500.12105/9709 27742545 10.1016/j.immuni.2016.09.012 1097-4180 Immunity Leishmania Uses Mincle to Target an Inhibitory ITAM Signaling Pathway in Dendritic Cells that Dampens Adaptive Immunity to Infection