Oral-resident natural Th17 cells and γδ T cells control opportunistic Candida albicans infections Article (Web of Science)


  • 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-7Rα−/−, 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 γδ T cells and CD3+CD4+CD44hiTCRβ+CCR6+ natural Th17 (nTh17) cells, but not by TCR-deficient innate lymphoid cells (ILCs) or NK cells. These cells function redundantly, as TCR-β−/− and TCR-δ−/− mice were both resistant to OPC. Whereas γδ 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-β clonal diversity, and was absent in Rag1−/−, IL-7Rα−/−, and germ-free mice. These findings indicate that nTh17 and γδ T cells, but not ILCs, are key mucosal sentinels that control oral pathogens.


  • Conti, Heather R
  • Peterson, Alanna C.
  • Brane, Lucas
  • Huppler, Anna R.
  • Hernández-Santos, Nydiaris
  • Whibley, Natasha
  • Garg, Abhishek V.
  • Simpson-Abelson, Michelle R.
  • Gibson, Gregory A.
  • Mamo, Anna J.
  • Osborne, Lisa C.
  • Bishu, Shrinivas
  • Ghilardi, Nico
  • Siebenlist, Ulrich
  • Watkins, Simon C.
  • Artis, David
  • McGeachy, Mandy J.
  • Gaffen, Sarah L.

publication date

  • 2014

published in

number of pages

  • 9

start page

  • 2075

end page

  • 2084


  • 211


  • 10