| First Author | Rani R | Year | 2012 |
| Journal | Am J Pathol | Volume | 180 |
| Issue | 5 | Pages | 2001-8 |
| PubMed ID | 22426339 | Mgi Jnum | J:183387 |
| Mgi Id | MGI:5318614 | Doi | 10.1016/j.ajpath.2012.01.013 |
| Citation | Rani R, et al. (2012) IFN-gamma-Driven IDO Production from Macrophages Protects IL-4Ralpha-Deficient Mice against Lethality during Schistosoma mansoni Infection. Am J Pathol 180(5):2001-8 |
| abstractText | The balance between alternatively activated macrophages (AAMs)/M2 cells and classically activated macrophages (M1 cells) is largely dependent on the effects of IL-4 and interferon (IFN)-gamma, respectively. Although AAM/M2 cells can suppress inflammation and repair damaged tissue, M1 cells produce an array of pro-inflammatory molecules. Macrophage effector functions are critical for host protection against many infectious diseases, but it remains unknown whether lethal immunopathological characteristics, caused by Schistosoma mansoni infection in IL-4 receptor alpha-deficient mice (IL-4Ralpha(-/-)), results from the absence of M2 cells or increased numbers of M1 cells. In this study, we generated mice that completely lack IL-4Ralpha signaling in the context of a macrophage-specific loss of IFN-gamma responsiveness (MIIG x IL-4Ralpha(-/-)). Contrary to what we expected, acute schistosomiasis resulted in greater liver injury and mortality in MIIG x IL-4Ralpha(-/-) mice compared with IL-4Ralpha(-/-) mice. Greater tissue injury in MIIG x IL-4Ralpha(-/-) mice was likely because of a lack of indoleamine 2,3 dioxygenase (IDO), a critical regulator of immunosuppression. Indeed, MIIG x IL-4Ralpha(-/-) failed to up-regulate IDO expression, and IL-4Ralpha(-/-) mice treated with an IDO antagonist underwent greater liver damage and mortality compared with mock-treated IL-4Ralpha(-/-) mice. Thus, we propose that, in the absence of AAM/M2 cells, IFN-gamma-induced M1 cells suppress tissue-damaging inflammation during acute schistosomiasis through an IDO-dependent mechanism. |
