PT  - JOURNAL ARTICLE
AU  - Lee, Youngae
AU  - Yamada, Hiroshi
AU  - Pradipta, Ariel
AU  - Ma, Ji Su
AU  - Okamoto, Masaaki
AU  - Nagaoka, Hikaru
AU  - Takashima, Eizo
AU  - Standley, Daron M
AU  - Sasai, Miwa
AU  - Takei, Kohji
AU  - Yamamoto, Masahiro
TI  - Initial phospholipid-dependent Irgb6 targeting to <em>Toxoplasma gondii</em> vacuoles mediates host defense
AID  - 10.26508/lsa.201900549
DP  - 2020 Jan 01
TA  - Life Science Alliance
PG  - e201900549
VI  - 3
IP  - 1
4099  - http://www.life-science-alliance.org/content/3/1/e201900549.short
4100  - http://www.life-science-alliance.org/content/3/1/e201900549.full
SO  - Life Sci. Alliance2020 Jan 01; 3
AB  - Toxoplasma gondii is an obligate intracellular protozoan parasite capable of infecting warm-blooded animals by ingestion. The organism enters host cells and resides in the cytoplasm in a membrane-bound parasitophorous vacuole (PV). Inducing an interferon response enables IFN-γ–inducible immunity-related GTPase (IRG protein) to accumulate on the PV and to restrict parasite growth. However, little is known about the mechanisms by which IRG proteins recognize and destroy T. gondii PV. We characterized the role of IRG protein Irgb6 in the cell-autonomous response against T. gondii, which involves vacuole ubiquitination and breakdown. We show that Irgb6 is capable of binding a specific phospholipid on the PV membrane. Furthermore, the absence of Irgb6 causes reduced targeting of other effector IRG proteins to the PV. This suggests that Irgb6 has a role as a pioneer in the process by which multiple IRG proteins access the PV. Irgb6-deficient mice are highly susceptible to infection by a strain of T. gondii avirulent in wild-type mice.