The Role of Dectin-2 for Host Defense Against Disseminated Candidiasis

Daniela C. Ifrim, Jessica Quintin, Flavie Courjol, Ineke Verschueren, J. Han van Krieken, Frank Koentgen, Chantal Fradin, Neil A. R. Gow, Leo A. B. Joosten, Jos W. M. van der Meer, Frank van de Veerdonk, Mihai G. Netea

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Abstract

Despite the fact that Candida albicans is an important human fungal pathogen and Dectin-2 is a major pattern recognition receptor for fungi, our knowledge regarding the role of Dectin-2 for the host defense against disseminated candidiasis is limited. Dectin-2 deficient (Dectin-2(-/-)) mice were more susceptible to systemic candidiasis, and the susceptibility was mirrored by an elevated fungal load in the kidneys that correlated with the presence of large inflammatory foci. Phagocytosis of Candida by the macrophages lacking the Dectin-2 receptor was moderately decreased, while production of most of the macrophage-derived cytokines from Dectin-2(-/-) mice with systemic candidiasis was decreased. No striking differences among several Candida mutants defective in mannans could be detected between naïve wild-type and Dectin-2(-/-) mice, apart from the β-mannan-deficient bmt1Δ/bmt2Δ/bmt5Δ triple mutant, suggesting that β-mannan may partially mask α-mannan detection, which is the major fungal structure recognized by Dectin-2. Deciphering the mechanisms responsible for host defense against the majority of C. albicans strains represents an important step in understanding the pathophysiology of systemic candidiasis, which might lead to the development of novel immunotherapeutic strategies.

Original languageEnglish
Pages (from-to)267-276
Number of pages10
JournalJournal of Interferon and Cytokine Research
Volume36
Issue number4
Early online date27 Jan 2016
DOIs
Publication statusPublished - 5 Apr 2016

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    Ifrim, D. C., Quintin, J., Courjol, F., Verschueren, I., van Krieken, J. H., Koentgen, F., Fradin, C., Gow, N. A. R., Joosten, L. A. B., van der Meer, J. W. M., van de Veerdonk, F., & Netea, M. G. (2016). The Role of Dectin-2 for Host Defense Against Disseminated Candidiasis. Journal of Interferon and Cytokine Research, 36(4), 267-276. https://doi.org/10.1089/jir.2015.0040