| Literature DB >> 25176311 |
Akiko Yonekawa1, Shinobu Saijo2, Yoshihiko Hoshino3, Yasunobu Miyake4, Eri Ishikawa4, Maho Suzukawa5, Hiromasa Inoue6, Masato Tanaka7, Mitsutoshi Yoneyama8, Masatsugu Oh-Hora9, Koichi Akashi10, Sho Yamasaki11.
Abstract
Mycobacteria possess various immunomodulatory molecules on the cell wall. Mannose-capped lipoarabinomannan (Man-LAM), a major lipoglycan of Mycobacterium tuberculosis, has long been known to have both inhibitory and stimulatory effects on host immunity. However, the direct Man-LAM receptor that explains its pleiotropic activities has not been clearly identified. Here, we report that a C-type lectin receptor Dectin-2 (gene symbol Clec4n) is a direct receptor for Man-LAM. Man-LAM activated bone-marrow-derived dendritic cells (BMDCs) to produce pro- and anti-inflammatory cytokines, whereas it was completely abrogated in Clec4n(-/-) BMDCs. Man-LAM promoted antigen-specific T cell responses through Dectin-2 on DCs. Furthermore, Man-LAM induced experimental autoimmune encephalitis (EAE) as an adjuvant in mice, whereas Clec4n(-/-) mice were resistant. Upon mycobacterial infection, Clec4n(-/-) mice showed augmented lung pathology. These results demonstrate that Dectin-2 contributes to host immunity against mycobacterial infection through the recognition of Man-LAM.Entities:
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Year: 2014 PMID： 25176311 DOI： 10.1016/j.immuni.2014.08.005
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745