| First Author | Schmidt S | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 12 | Pages | e52211 |
| PubMed ID | 23284939 | Mgi Jnum | J:195616 |
| Mgi Id | MGI:5484939 | Doi | 10.1371/journal.pone.0052211 |
| Citation | Schmidt S, et al. (2012) Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice. PLoS One 7(12):e52211 |
| abstractText | Gut-dwelling helminthes induce potent IL-4 and IL-13 dominated type 2 T helper cell (T(H)2) immune responses, with IL-13 production being essential for Nippostrongylus brasiliensis expulsion. This T(H)2 response results in intestinal inflammation associated with local infiltration by T cells and macrophages. The resulting increased IL-4/IL-13 intestinal milieu drives goblet cell hyperplasia, alternative macrophage activation and smooth muscle cell hypercontraction. In this study we investigated how IL-4-promoted T cells contributed to the parasite induced effects in the intestine. This was achieved using pan T cell-specific IL-4 receptor alpha-deficient mice (iLck(cre)IL-4Ralpha(-/lox)) and IL-4Ralpha-responsive control mice. Global IL-4Ralpha(-/-) mice showed, as expected, impaired type 2 immunity to N. brasiliensis. Infected T cell-specific IL-4Ralpha-deficient mice showed comparable worm expulsion, goblet cell hyperplasia and IgE responses to control mice. However, impaired IL-4-promoted T(H)2 cells in T cell-specific IL-4Ralpha deficient mice led to strikingly reduced IL-4 production by mesenteric lymph node CD4(+) T cells and reduced intestinal IL-4 and IL-13 levels, compared to control mice. This reduced IL-4/IL-13 response was associated with an impaired IL-4/IL-13-mediated smooth muscle cell hypercontractility, similar to that seen in global IL-4Ralpha(-/-) mice. These results demonstrate that IL-4-promoted T cell responses are not required for the resolution of a primary N. brasiliensis infection. However, they do contribute significantly to an important physiological manifestation of helminth infection; namely intestinal smooth muscle cell-driven hypercontractility. |
