| First Author | Matsuzawa T | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 2 | Pages | 813-8 |
| PubMed ID | 22675202 | Mgi Jnum | J:189560 |
| Mgi Id | MGI:5446109 | Doi | 10.4049/jimmunol.1102041 |
| Citation | Matsuzawa T, et al. (2012) IFN-gamma elicits macrophage autophagy via the p38 MAPK signaling pathway. J Immunol 189(2):813-8 |
| abstractText | Autophagy is a major innate immune defense pathway in both plants and animals. In mammals, this cascade can be elicited by cytokines (IFN-gamma) 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-gamma 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-gamma-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-gamma-induced autophagy is mobilized within macrophages for inflammation and host defense. |
