Initial phospholipid-dependent Irgb6 targeting to Toxoplasma gondii vacuoles mediates host defense

Youngae Lee, Hiroshi Yamada, Ariel Pradipta, Ji Su Ma, Masaaki Okamoto, Hikaru Nagaoka, Eizo Takashima, Daron M. Standley, Miwa Sasai, Kohji Takei, Masahiro Yamamoto

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Abstract

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.

Original languageEnglish
Article numbere201900549
JournalLife Science Alliance
Volume3
Issue number1
DOIs
Publication statusPublished - Jan 1 2020

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ASJC Scopus subject areas

  • Ecology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Plant Science
  • Health, Toxicology and Mutagenesis

Cite this

Lee, Y., Yamada, H., Pradipta, A., Ma, J. S., Okamoto, M., Nagaoka, H., Takashima, E., Standley, D. M., Sasai, M., Takei, K., & Yamamoto, M. (2020). Initial phospholipid-dependent Irgb6 targeting to Toxoplasma gondii vacuoles mediates host defense. Life Science Alliance, 3(1), [e201900549]. https://doi.org/10.26508/lsa.201900549