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Título
Leishmania Uses Mincle to Target an Inhibitory ITAM Signaling Pathway in Dendritic Cells that Dampens Adaptive Immunity to Infection
Autor(es)
Iborra, Salvador CNIC | Martinez-Lopez, Maria CNIC | Cueto, Francisco J. CNIC | Conde-Garrosa, Ruth CNIC | del Fresno, Carlos CNIC | Izquierdo-Fernandez, Helena Maria CNIC | Abram, Clare L | Mori, Daiki | Campos-Martín, Yolanda | Reguera, Rosa María | Kemp, Benjamin | Yamasaki, Sho | Robinson, Matthew J | Soto, Manuel | Lowell, Clifford A | Sancho, David CNIC
Fecha de publicación
2016-10
Cita
Immunity. 2016; 45(4):788-801
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
MESH
Adaptive Immunity | Animals | CD11c Antigen | Cell Differentiation | Cell Line, Tumor | Dendritic Cells | Immunoreceptor Tyrosine-Based Activation Motif | Lectins, C-Type | Leishmania major | Membrane Proteins | Mice | Mice, Inbred C57BL | Mice, Transgenic | Protein Tyrosine Phosphatase, Non-Receptor Type 6 | Receptors, Fc | Signal Transduction
Versión en línea
DOI
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