論文 - 詳細
| RRC ID | 47496 |
|---|---|
| 著者 | Iborra S, Martínez-López M, Cueto FJ, Conde-Garrosa R, Del Fresno C, Izquierdo HM, Abram CL, Mori D, Campos-Martín Y, Reguera RM, Kemp B, Yamasaki S, Robinson MJ, Soto M, Lowell CA, Sancho D. |
| タイトル | Leishmania Uses Mincle to Target an Inhibitory ITAM Signaling Pathway in Dendritic Cells that Dampens Adaptive Immunity to Infection. |
| ジャーナル | Immunity |
| Abstract |
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. |
| 巻・号 | 45(4) |
| ページ | 788-801 |
| 公開日 | 2016-10-18 |
| DOI | 10.1016/j.immuni.2016.09.012 |
| PII | S1074-7613(16)30381-8 |
| PMID | 27742545 |
| PMC | PMC5074365 |
| MeSH | Adaptive Immunity / immunology* Animals CD11c Antigen / immunology Cell Differentiation / immunology Cell Line, Tumor Dendritic Cells / immunology* Immunoreceptor Tyrosine-Based Activation Motif / immunology* Lectins, C-Type / immunology* Leishmania major / immunology* Membrane Proteins / immunology* Mice Mice, Inbred C57BL Mice, Transgenic Protein Tyrosine Phosphatase, Non-Receptor Type 6 / immunology Receptors, Fc / immunology Signal Transduction / immunology* |
| IF | 22.553 |
| 引用数 | 40 |
| WOS 分野 | IMMUNOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 49 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | CSII-CMV-MCS-IRES2-Bsd (RDB04385) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393). |