Guanylate-binding Protein 1 (Gbp1) Contributes to Cell-autonomous Immunity Against Toxoplasma Gondii

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2013 May 2

PMID 23633952

Citations 116

Authors

Elizabeth M Selleck

Sarah J Fentress

Wandy L Beatty

Daniel Degrandi

Klaus Pfeffer

Herbert W Virgin 4th

John D MacMicking

L David Sibley

Affiliations

Soon will be listed here.

Abstract

IFN-γ activates cells to restrict intracellular pathogens by upregulating cellular effectors including the p65 family of guanylate-binding proteins (GBPs). Here we test the role of Gbp1 in the IFN-γ-dependent control of T. gondii in the mouse model. Virulent strains of T. gondii avoided recruitment of Gbp1 to the parasitophorous vacuole in a strain-dependent manner that was mediated by the parasite virulence factors ROP18, an active serine/threonine kinase, and the pseudokinase ROP5. Increased recruitment of Gbp1 to Δrop18 or Δrop5 parasites was associated with clearance in IFN-γ-activated macrophages in vitro, a process dependent on the autophagy protein Atg5. The increased susceptibility of Δrop18 mutants in IFN-γ-activated macrophages was reverted in Gbp1(-/-) cells, and decreased virulence of this mutant was compensated in Gbp1(-/-) mice, which were also more susceptible to challenge with type II strain parasites of intermediate virulence. These findings demonstrate that Gbp1 plays an important role in the IFN-γ-dependent, cell-autonomous control of toxoplasmosis and predict a broader role for this protein in host defense.

Citing Articles

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