Analysis of IFN-inducible GTPase-dependent cell-autonomous immunity

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04745
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: Yamamoto Masahiro 大阪大学, 微生物病研究所, 教授 (00444521)
• Research Collaborator: SASAI Miwa
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: インターフェロン / トキソプラズマ / 病原体

Outline of Final Research Achievements

Mammalian Atg8 homologs consist of LC3 proteins and GABARAPs, all of which are known to be involved in canonical autophagy. In contrast, the roles of Atg8 homologs in noncanonical autophagic processes are not fully understood. Here we show a unique role of GABARAPs, in particular Gate-16, in IFN-γ-mediated antimicrobial responses. Cells that lacked GABARAPs but not LC3 proteins and mice that lacked Gate-16 alone were defective in the IFN-γ-induced clearance of vacuolar pathogens such as Toxoplasma. Gate-16 but not LC3b specifically associated with the small GTPase Arf1 to mediate uniform distribution of interferon-inducible GTPases. The lack of GABARAPs reduced Arf1 activation, which led to formation of interferon-inducible GTPase-containing aggregates and hampered recruitment of interferon-inducible GTPases to vacuolar pathogens. Thus, GABARAPs are uniquely required for antimicrobial host defense through cytosolic distribution of interferon-inducible GTPases.

Free Research Field

寄生虫免疫学