T Helper 2 Cytokines Inhibit Autophagic Control of Intracellular Mycobacterium tuberculosis

Harris, J., et al. 2007. Immunity. 27: 505-517

Speaker: 李婉綺                                                   Time: 15:10-16:00, May. 21, 2008

Commentator: 徐麗君 博士                                Place: Room 601

Abstract:

        Autophagy has recently been shown to be an important component of innate immune response. It has been shown the T helper 1 (Th1) cell cytokine IFN-γ induces autophagy in macrophages to eliminate intracellular pathogens Mycobacterium tuberculosis (1) Although the role of autophagy in innate immunity has been well established, the extent of its regulation by the adaptive immune response is less well understood. In this study (2), the author demonstrates that Th2 cytokines, IL-4 and Il-13 have antagonistic effects on autophagy, hence to inhibit the Th1-dependent protection against intracellular M. tuberculosis. In addition, IL-4 and IL-13 inhibit starvation-induced autophagy which was dependent on AKT signaling, whereas the inhibition of IFN-γ-induced autophagy was AKT independent and activator of transcription 6 (STAT6) dependent. This study reveals a novel role of Th1-Th2 polarization, which modulating autophagy as an immune effector mechanism to control intracellular pathogens.

References:

1.      Gutieerez, M.G., e al. 2004. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119: 753-766.

2.      Harris, J., et al. 2007. T helper 2 cytokines inhibit autophagic control of intracellular Mycobacterium tuberculosis. Immunity 27: 505-517.