Autophagic Elimination of Intracellular Parasites: Convergent Induction by IFN-gamma and CD40 Ligation?

George S. Yap, Yun Ling and Yanlin Zhao

volume 3 | issue 2

March/April 2007
Pages: 163 - 165

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Autophagy has recently been implicated in the immune elimination of the intracellular protozoan parasite, Toxoplasma gondii. Toxoplasma and other apicomplexan parasites actively invade host cells and form non-fusogenic parasitophorous vacuoles. Nevertheless, following entry into IFN-gamma-activated effector macrophages, vesiculation of the parasite vacuole or PV membrane ensues, in a process dependent upon the activity of p47 GTPases induced by IFN-gamma signaling. Subsequent disruption of the plasma membrane of the stripped parasites precedes autophagolysosomal elimination of T. gondii. In contrast, ligation of the CD40 receptor and autocrine signaling by TNF activate a seemingly distinct, p47 GTPase-independent mechanism leading to autophagic elimination of intracellular T. gondii, without prior disruption of the pathogen vacuole. Thus, two key pathways of the cell-mediated immune response, namely IFN-gamma and CD40/CD40L, trigger a common autophagolysosomal endpoint of parasite elimination, via distinct intermediary mechanisms.

Addendum to:
Vacuolar and Plasma Membrane Stripping and Autophagic Elimination of Toxoplasma gondii in Primed Effector Macrophages
Y.M. Ling, M.H. Shaw, C. Ayala, I. Coppens, G.A. Taylor, D.J. Ferguson, and G.S. Yap
J Exper Med 2006; 203:2063-71

Authors

George S. Yap

University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Yun Ling

Brown University

Yanlin Zhao