Guanylate-binding Protein 1 (Gbp1) Contributes to Cell-autonomous Immunity against Toxoplasma gondii

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. © 2013 selleck et al.