2024-03-29T08:57:49Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/97092023-10-06T16:09:40Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144col_20.500.12105_2146
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