Dectin-2 is a direct receptor for mannose-capped lipoarabinomannan of mycobacteria

Akiko Yonekawa, Shinobu Saijo, Yoshihiko Hoshino, Yasunobu Miyake, Eri Ishikawa, Maho Suzukawa, Hiromasa Inoue, Masato Tanaka, Mitsutoshi Yoneyama, Masatsugu Oh-hora, Koichi Akashi, Sho Yamasaki

Research output: Contribution to journalArticlepeer-review

155 Citations (Scopus)

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 Tcell 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.

Original languageEnglish
Pages (from-to)402-413
Number of pages12
JournalImmunity
Volume41
Issue number3
DOIs
Publication statusPublished - Sep 18 2014

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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