The Adaptor CARD9 Is Required for Adaptive but Not Innate Immunity to Oral Mucosal Candida albicans Infections Article (Web of Science)

abstract

  • ABSTRACTOropharyngeal candidiasis (OPC [thrush]) is an opportunistic infection caused by the commensal fungusCandida albicans. OPC is common in individuals with HIV/AIDS, infants, patients on chemotherapy, and individuals with congenital immune defects. Immunity to OPC is strongly dependent on the interleukin-23 (IL-23)/IL-17R axis, as mice and humans with defects in IL-17R signaling (IL17F,ACT1,IL-17RA) or in genes that direct Th17 differentiation (STAT3,STAT1,CARD9) are prone to mucocutaneous candidiasis. Conventional Th17 cells are induced in response toC. albicansinfection via signals from C-type lectin receptors, which signal through the adaptor CARD9, leading to production of Th17-inducing cytokines such as IL-6, IL-1β, and IL-23. Recent data indicate that IL-17 can also be made by numerous innate cell subsets. These innate “type 17” cells resemble conventional Th17 cells, but they can be activated without need for prior antigen exposure. BecauseC. albicansis not a commensal organism in rodents and mice are thus naive to this fungus, we had the opportunity to assess the role of CARD9 in innate versus adaptive responses using an OPC infection model. As expected, CARD9−/−mice failed to mount an adaptive Th17 response following oralCandidainfection. Surprisingly, however, CARD9−/−mice had preserved innate IL-17-dependent responses toCandidaand were almost fully resistant to OPC. Thus, CARD9 is important primarily for adaptive immunity toC. albicans, whereas alternate recognition systems appear to be needed for effective innate responses.

authors

  • Bishu, Shrinivas
  • Hernández-Santos, Nydiaris
  • Simpson-Abelson, Michelle R.
  • Huppler, Anna R.
  • Conti, Heather R
  • Ghilardi, Nico
  • Mamo, Anna J.
  • Gaffen, Sarah L.

publication date

  • 2014

webpage

published in

number of pages

  • 7

start page

  • 1173

end page

  • 1180

volume

  • 82

issue

  • 3