CD40-TRAF6 and Autophagy-Dependent Anti-Microbial Activity in Macprophages

Autophagy. 2007 May 15;3(3) [Epub ahead of print]

CD40-TRAF6 and Autophagy-Dependent Anti-Microbial Activity in Macprophages.

Subauste CS, Andrade RM, Wessendarp M.

Departments of Ophthalmology and Medicine, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USA.

A fundamental question in host-pathogen interaction is to determine if the immune system activates fusion with the lysosomes to eradicate pathogens. We recently reported that this task is accomplished by the interaction between CD40 expressed on macrophages and CD154 expressed on activated CD4(+) T cells. CD40 stimulation of macrophages induces vacuole-lysosome fusion through autophagy and results in killing of the obligate intracellular pathogen Toxoplasma gondii. This response is independent of IFN-gamma, STAT1 and p47 GTPases. We now report that vacuole-lysosome fusion is dependent on synergy between TRAF6 signaling downstream of CD40 and TNF-alpha. These studies identified a new paradigm by which T cells eradicate an intracellular pathogen within macrophages.

PMID: 17224624 [PubMed - as supplied by publisher]