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.
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http://dx.doi.org/10.1128/IAI.01335-13 | DOI Listing |
J Biol Chem
November 2024
Department of Genome Science and Microbiology, Faculty of Medical Sciences, University of Fukui, Eiheiji, Fukui, Japan; Life Science Innovation Center, University of Fukui, Fukui, Fukui, Japan.
Dectin-1, a C-type lectin, plays important roles in the induction of antifungal immunity. Caspase recruitment domain-containing protein 9 (CARD9) is essential for the dectin-1-induced production of cytokines through the activation of NF-κB. However, the molecular mechanisms underlying the dectin-1-mediated activation of CARD9 have not been fully elucidated.
View Article and Find Full Text PDFDev Comp Immunol
November 2024
Department of Biological Sciences, Clemson University, Clemson, SC, USA; Eukaryotic Pathogens Innovation Center, Clemson University, Clemson, SC, USA. Electronic address:
Pattern recognition receptors (PRRs) such as C-type lectin receptors (CLRs) and Toll-like receptors (TLRs) are used by hosts to recognize pathogen-associated molecular patterns (PAMPs) in microorganisms and to initiate innate immune responses. While PRRs exist across invertebrate and vertebrate species, the functional homology of many of these receptors is still unclear. In this study, we investigate the innate immune response of zebrafish larvae to zymosan, a β-glucan-containing particle derived from fungal cell walls.
View Article and Find Full Text PDFJ Cell Mol Med
November 2024
Department of Medicine, Hunan Traditional Chinese Medical College, Zhuzhou, Hunan, People's Republic of China.
Myocardial injury induced by ischemia-reperfusion (I/R) remains a difficult clinical problem. However, the exact mechanisms underlying I/R-induced have yet to be clarified. CARD9 is an important cytoplasmic-binding protein.
View Article and Find Full Text PDFInt Immunopharmacol
December 2024
Department of Hepatobiliary Pancreatic Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei, Anhui Province 230022, China. Electronic address:
Cholangiocarcinoma (CCA) is a highly lethal malignant tumor originating from the bile duct, and its underlying mechanisms are not fully understood. In order to identify key genes in CCA, we downloaded gene expression data from public GSE76297, GSE26566 and TCGA-CHOL datasets. CARD9 was selected as a CCA-related gene from the datasets.
View Article and Find Full Text PDFHeliyon
October 2024
Department of Immunology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima-City, Kagoshima, 890-8544, Japan.
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