IFN-γ elicits macrophage autophagy via the p38 MAPK signaling pathway.

Abstract

Autophagy is a major innate immune defense pathway in both plants and animals. In mammals, this cascade can be elicited by cytokines (IFN-γ) or pattern recognition receptors (TLRs and nucleotide-binding oligomerization domain-like receptors). Many signaling components in TLR- and nucleotide-binding oligomerization domain-like receptor-induced autophagy are now known; however, those involved in activating autophagy via IFN-γ remain to be elucidated. In this study, we engineered macrophages encoding a tandem fluorescently tagged LC3b (tfLC3) autophagosome reporter along with stably integrated short hairpin RNAs to demonstrate IFN-γ-induced autophagy required JAK 1/2, PI3K, and p38 MAPK but not STAT1. Moreover, the autophagy-related guanosine triphosphatase Irgm1 proved dispensable in both stable tfLC3-expressing RAW 264.7 and tfLC3-transduced Irgm1(-/-) primary macrophages, revealing a novel p38 MAPK-dependent, STAT1-independent autophagy pathway that bypasses Irgm1. These unexpected findings have implications for understanding how IFN-γ-induced autophagy is mobilized within macrophages for inflammation and host defense.

DOI: 10.4049/jimmunol.1102041

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@article{Matsuzawa2012IFNEM, title={IFN-γ elicits macrophage autophagy via the p38 MAPK signaling pathway.}, author={Takeshi Matsuzawa and Bae-Hoon Kim and Avinash R Shenoy and Shigeki Kamitani and Masami Miyake and John D Macmicking}, journal={Journal of immunology}, year={2012}, volume={189 2}, pages={813-8} }