Role of p62-related autophagy adaptor proteins in anti-microbial host defense

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19153
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: Lee Youngae 大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (60610681)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: オートファジー / アダプター / 獲得免疫

Outline of Final Research Achievements

We show that interferon γ (IFN-γ) stimulates ubiquitin and p62 recruitment to T. gondii parasitophorous vacuoles (PVs). Some essential autophagy-related proteins, but not all, are required for this recruitment. Regardless of normal IFN-γ-induced T. gondii clearance activity and ubiquitination, p62 deficiency in antigen-presenting cells (APCs) and mice diminishes the robust IFN-γ-primed activation of CD8+ T cells that recognize the T. gondii-derived antigen secreted into PVs. Because the expression of Atg3 and Irgm1/m3 in APCs is essential for PV disruption, ubiquitin and p62 recruitment, and vacuolar-antigen-specific CD8+ T cell activation, IFN-γ-mediated ubiquitination and the subsequent recruitment of p62 to T. gondii are specifically required for the acquired immune response after PV disruption by IFN-γ-inducible GTPases.

Free Research Field

免疫学