Faculty Collaboration Database

The adaptor CARD9 is required for adaptive but not innate immunity to oral mucosal Candida albicans infections. Infect Immun 2014 Mar;82(3):1173-80

Date

01/01/2014

Pubmed ID

24379290

Pubmed Central ID

PMC3958019

DOI

10.1128/IAI.01335-13

Scopus ID

2-s2.0-84894271473 (requires institutional sign-in at Scopus site)   50 Citations

Abstract

Oropharyngeal candidiasis (OPC [thrush]) is an opportunistic infection caused by the commensal fungus Candida 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 to C. albicans infection 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. Because C. albicans is 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 oral Candida infection. Surprisingly, however, CARD9(-/-) mice had preserved innate IL-17-dependent responses to Candida and were almost fully resistant to OPC. Thus, CARD9 is important primarily for adaptive immunity to C. albicans, whereas alternate recognition systems appear to be needed for effective innate responses.

Author List

Bishu S, Hernández-Santos N, Simpson-Abelson MR, Huppler AR, Conti HR, Ghilardi N, Mamo AJ, Gaffen SL

Author

Anna H. Huppler MD Associate Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adaptive Immunity
Adaptor Proteins, Signal Transducing
Animals
CARD Signaling Adaptor Proteins
Candida albicans
Candidiasis
Gastrointestinal Tract
Immunity, Innate
Interleukin-17
Mice
Mice, Inbred C57BL
Mouth Mucosa
Th17 Cells