CD40-TRAF6 and autophagy-dependent anti-microbial activity in macrophages

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 ce...

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Bibliographic Details
Published in:Autophagy 2007-05, Vol.3 (3), p.245-248
Main Authors: Subauste, Carlos S, Andrade, Rosa M, Wessendarp, Matthew
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Autophagy - immunology
CD40 Antigens - genetics
CD40 Antigens - immunology
CD40 Ligand - genetics
CD40 Ligand - immunology
Humans
Lysosomes - metabolism
Macrophages - cytology
Macrophages - immunology
Macrophages - parasitology
Mice
Molecular Sequence Data
Recombinant Fusion Proteins
Signal Transduction
T-Lymphocytes - immunology
TNF Receptor-Associated Factor 6 - metabolism
Toxoplasma - immunology
Tumor Necrosis Factor-alpha - metabolism
Vacuoles - metabolism
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Summary: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.
ISSN:1554-8627
DOI:10.4161/auto.3717