RT Journal Article SR Electronic T1 Initial phospholipid-dependent Irgb6 targeting to Toxoplasma gondii vacuoles mediates host defense JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e201900549 DO 10.26508/lsa.201900549 VO 3 IS 1 A1 Lee, Youngae A1 Yamada, Hiroshi A1 Pradipta, Ariel A1 Ma, Ji Su A1 Okamoto, Masaaki A1 Nagaoka, Hikaru A1 Takashima, Eizo A1 Standley, Daron M A1 Sasai, Miwa A1 Takei, Kohji A1 Yamamoto, Masahiro YR 2020 UL http://www.life-science-alliance.org/content/3/1/e201900549.abstract 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.