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Autophagy. 2007 Mar-Apr;3(2):163-5. Epub 2007 Mar 5.

Autophagic elimination of intracellular parasites: convergent induction by IFN-gamma and CD40 ligation?

Author information

1
Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island 02912, USA. George_Yap@Brown.edu

Abstract

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 nonfusogenic 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.

PMID:
17204853
[Indexed for MEDLINE]

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