Host cell autophagy Is induced by toxoplasma gondii and contributes to parasite growth

Yubao Wang, Louis M. Weiss, Amos Orlofsky

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Autophagy has been shown to contribute to defense against intracellular bacteria and parasites. In comparison, the ability of such pathogens to manipulate host cell autophagy to their advantage has not been examined. Here we present evidence that infection by Toxoplasma gondii, an intracellular protozoan parasite, induces host cell autophagy in both HeLa cells and primary fibroblasts, via a mechanism dependent on host Atg5 but independent of host mammalian target of rapamycin suppression. Infection led to the conversion of LC3 to the autophagosome-associated form LC3-II, to the accumulation of LC3-containing vesicles near the parasitophorous vacuole, and to the relocalization toward the vacuole of structures labeled by the phosphatidylinositol 3-phosphate indicator YFP-2 × FYVE. The autophagy regulator beclin 1 was concentrated in the vicinity of the parasitophorous vacuole in infected cells. Inhibitor studies indicated that parasite-induced autophagy is dependent on calcium signaling and on abscisic acid. At physiologically relevant amino acid levels, parasite growth became defective in Atg5-deficient cells, indicating a role for host cell autophagy in parasite recovery of host cell nutrients. A flow cytometric analysis of cell size as a function of parasite content revealed that autophagy-dependent parasite growth correlates with autophagy-dependent consumption of host cell mass that is dependent on parasite progression. These findings indicate a new role for autophagy as a pathway by which parasites may effectively compete with the host cell for limiting anabolic resources.

Original languageEnglish (US)
Pages (from-to)1694-1701
Number of pages8
JournalJournal of Biological Chemistry
Volume284
Issue number3
DOIs
StatePublished - Jan 16 2009

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Autophagy
Toxoplasma
Parasites
Growth
Vacuoles
Abscisic Acid
Calcium Signaling
Toxoplasmosis
Pathogens
Sirolimus
Fibroblasts
Cell Size
HeLa Cells
Nutrients
Bacteria
Calcium
Amino Acids
Recovery
Food
Infection

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Host cell autophagy Is induced by toxoplasma gondii and contributes to parasite growth. / Wang, Yubao; Weiss, Louis M.; Orlofsky, Amos.

In: Journal of Biological Chemistry, Vol. 284, No. 3, 16.01.2009, p. 1694-1701.

Research output: Contribution to journalArticle

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