| First Author | Moreira-Teixeira L | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 2 | Pages | 613-623 |
| PubMed ID | 28584007 | Mgi Jnum | J:251503 |
| Mgi Id | MGI:6099863 | Doi | 10.4049/jimmunol.1601340 |
| Citation | Moreira-Teixeira L, et al. (2017) T Cell-Derived IL-10 Impairs Host Resistance to Mycobacterium tuberculosis Infection. J Immunol 199(2):613-623 |
| abstractText | Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, is a leading cause of mortality and morbidity, causing approximately 1.5 million deaths annually. CD4(+) T cells and several cytokines, such as the Th1 cytokine IFN-gamma, are critical in the control of this infection. Conversely, the immunosuppressive cytokine IL-10 has been shown to dampen Th1 cell responses to M. tuberculosis infection impairing bacterial clearance. However, the critical cellular source of IL-10 during M. tuberculosis infection is still unknown. Using IL-10 reporter mice, we show in this article that during the first 14 d of M. tuberculosis infection, the predominant cells expressing IL-10 in the lung were Ly6C(+) monocytes. However, after day 21 postinfection, IL-10-expressing T cells were also highly represented. Notably, mice deficient in T cell-derived IL-10, but not mice deficient in monocyte-derived IL-10, showed a significant reduction in lung bacterial loads during chronic M. tuberculosis infection compared with fully IL-10-competent mice, indicating a major role for T cell-derived IL-10 in TB susceptibility. IL-10-expressing cells were detected among both CD4(+) and CD8(+) T cells, expressed high levels of CD44 and Tbet, and were able to coproduce IFN-gamma and IL-10 upon ex vivo stimulation. Furthermore, during M. tuberculosis infection, Il10 expression in CD4(+) T cells was partially regulated by both IL-27 and type I IFN signaling. Together, our data reveal that, despite the multiple immune sources of IL-10 during M. tuberculosis infection, activated effector T cells are the major source accounting for IL-10-induced TB susceptibility. |
