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Publication : T helper 2 cytokines inhibit autophagic control of intracellular Mycobacterium tuberculosis.

First Author  Harris J Year  2007
Journal  Immunity Volume  27
Issue  3 Pages  505-17
PubMed ID  17892853 Mgi Jnum  J:125301
Mgi Id  MGI:3758143 Doi  10.1016/j.immuni.2007.07.022
Citation  Harris J, et al. (2007) T helper 2 cytokines inhibit autophagic control of intracellular Mycobacterium tuberculosis. Immunity 27(3):505-17
abstractText  Autophagy is a recently recognized immune effector mechanism against intracellular pathogens. The role of autophagy in innate immunity has been well established, but the extent of its regulation by the adaptive immune response is less well understood. The T helper 1 (Th1) cell cytokine IFN-gamma induces autophagy in macrophages to eliminate Mycobacterium tuberculosis. Here, we report that Th2 cytokines affect autophagy in macrophages and their ability to control intracellular M. tuberculosis. IL-4 and IL-13 abrogated autophagy and autophagy-mediated killing of intracellular mycobacteria in murine and human macrophages. Inhibition of starvation-induced autophagy by IL-4 and IL-13 was dependent on Akt signaling, whereas the inhibition of IFN-gamma-induced autophagy was Akt independent and signal transducer and activator of transcription 6 (STAT6) dependent. These findings establish a mechanism through which Th1-Th2 polarization differentially affects the immune control of intracellular pathogens.
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