| First Author | Conti HR | Year | 2014 |
| Journal | J Exp Med | Volume | 211 |
| Issue | 10 | Pages | 2075-84 |
| PubMed ID | 25200028 | Mgi Jnum | J:218689 |
| Mgi Id | MGI:5618199 | Doi | 10.1084/jem.20130877 |
| Citation | Conti HR, et al. (2014) Oral-resident natural Th17 cells and gammadelta T cells control opportunistic Candida albicans infections. J Exp Med 211(10):2075-84 |
| abstractText | Oropharyngeal candidiasis (OPC) is an opportunistic fungal infection caused by Candida albicans. OPC is frequent in HIV/AIDS, implicating adaptive immunity. Mice are naive to Candida, yet IL-17 is induced within 24 h of infection, and susceptibility is strongly dependent on IL-17R signaling. We sought to identify the source of IL-17 during the early innate response to candidiasis. We show that innate responses to Candida require an intact TCR, as SCID, IL-7Ralpha(-/-), and Rag1(-/-) mice were susceptible to OPC, and blockade of TCR signaling by cyclosporine induced susceptibility. Using fate-tracking IL-17 reporter mice, we found that IL-17 is produced within 1-2 d by tongue-resident populations of gammadelta T cells and CD3(+)CD4(+)CD44(hi)TCRbeta(+)CCR6(+) natural Th17 (nTh17) cells, but not by TCR-deficient innate lymphoid cells (ILCs) or NK cells. These cells function redundantly, as TCR-beta(-/-) and TCR-delta(-/-) mice were both resistant to OPC. Whereas gammadelta T cells were previously shown to produce IL-17 during dermal candidiasis and are known to mediate host defense at mucosal surfaces, nTh17 cells are poorly understood. The oral nTh17 population expanded rapidly after OPC, exhibited high TCR-beta clonal diversity, and was absent in Rag1(-/-), IL-7Ralpha(-/-), and germ-free mice. These findings indicate that nTh17 and gammadelta T cells, but not ILCs, are key mucosal sentinels that control oral pathogens. |
