T Helper 2 Cytokines Inhibit Autophagic Control of Intracellular Mycobacterium tuberculosis

Abstract

Autophagy is a recently recognized immune effect or 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 responseis less well understood. The T helper 1 (Th1) cell cytokine IFN-γ induces autophagy in macrophages to eliminateMycobacterium tuberculosis. Here, we report that Th2 cytokines affect autophagy in macrophages and their ability tocontrol intracellularM. tuberculosis. IL-4 andIL-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-γ-induced 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.