| First Author | Keestra AM | Year | 2011 |
| Journal | Infect Immun | Volume | 79 |
| Issue | 8 | Pages | 3131-40 |
| PubMed ID | 21576324 | Mgi Jnum | J:175270 |
| Mgi Id | MGI:5285050 | Doi | 10.1128/IAI.00018-11 |
| Citation | Keestra AM, et al. (2011) Early MyD88-dependent induction of interleukin-17A expression during Salmonella colitis. Infect Immun 79(8):3131-40 |
| abstractText | The development of T helper 17 (T(H)17) cells is a well-established adaptive mechanism for the production of interleukin-17A (IL-17A), a cytokine involved in neutrophil recruitment. However, pathways contributing to mucosal expression of IL-17A during the initial phase of a bacterial infection have received less attention. Here we used the mouse colitis model of Salmonella enterica serotype Typhimurium infection to investigate the contribution of myeloid differentiation primary response protein 88 (MyD88) to inflammation and mucosal IL-17A expression. Expression of IL-23 in the cecal mucosa during S. Typhimurium colitis was dependent on the presence of MyD88. Furthermore, initial expression of IL-17A at 24 h after S. Typhimurium infection was dependent on MyD88 and the receptor for IL-1beta. IL-23 and IL-1beta synergized in inducing expression of IL-17A in splenic T cells in vitro. In the intestinal mucosa, IL-17A was produced by three distinct T cell populations, including deltagamma T cells, T(H)17 cells, and CD4(-)CD8(-) T cells. The absence of IL-1beta signaling or IL-17 signaling reduced CXC chemokine expression but did not alter the overall severity of pathological lesions in the cecal mucosa. In contrast, cecal pathology and neutrophil recruitment were markedly reduced in Myd88-deficient mice during the initial phases of S. Typhimurium infection. Collectively, these data demonstrate that MyD88-dependent mechanisms, including an initial expression of IL-17A, are important for orchestrating early inflammatory responses during S. Typhimurium colitis. |
