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Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis

Cellular & Molecular Immunology volume 9, pages 276–286 (2012)Cite this article

Abstract

The recognition of β-glucans by dectin-1 has been shown to mediate cell activation, cytokine production and a variety of antifungal responses. Here, we report that the functional activity of dectin-1 in mucosal immunity to Candida albicans is influenced by the genetic background of the host. Dectin-1 was required for the proper control of gastrointestinal and vaginal candidiasis in C57BL/6, but not BALB/c mice; in fact, the latter showed increased resistance in the absence of dectin-1. The susceptibility of dectin-1-deficient C57BL/6 mice to infection was associated with defects in IL-17A and aryl hydrocarbon receptor-dependent IL-22 production and in adaptive Th1 responses. In contrast, the resistance of dectin-1-deficient BALB/c mice was associated with increased IL-17A and IL-22 production and the skewing towards Th1/Treg immune responses that provide immunological memory. Disparate canonical/noncanonical NF-κB signaling pathways downstream of dectin-1 were activated in the two different mouse strains. Thus, the net activity of dectin-1 in antifungal mucosal immunity is dependent on the host's genetic background, which affects both the innate cytokine production and the adaptive Th1/Th17 cell activation upon dectin-1 signaling.

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Acknowledgements

We thank Dr Cristina Massi Benedetti for the digital art and editing. The studies were supported by the Specific Targeted Research Project ‘ALLFUN’ (FP7-HEALTH-2009 contract no. 260338 to LR) and the Italian Project AIDS 2010 by ISS (Istituto Superiore di Sanità contract no. 40H40 to LR) and Fondazione Cassa di Risparmio di Perugia Project no. 2011.0124.021. AC and CC were financially supported by fellowships from Fundação para a Ciência e Tecnologia, Portugal (contracts SFRH/BPD/46292/2008 and SFRH/BD/65962/2009, respectively).

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Authors and Affiliations

  1. Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy

    Agostinho Carvalho, Gloria Giovannini, Antonella De Luca, Carmen D'Angelo, Andrea Casagrande, Rossana G Iannitti, Giovanni Ricci, Cristina Cunha & Luigina Romani

  2. Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal

    Agostinho Carvalho

  3. ICVS/3B's—PT Government Associate Laboratory, Braga/Guimarães, Portugal

    Agostinho Carvalho

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  1. Agostinho Carvalho
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  2. Gloria Giovannini
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  3. Antonella De Luca
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Correspondence to Luigina Romani.

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Carvalho, A., Giovannini, G., De Luca, A. et al. Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis. Cell Mol Immunol 9, 276–286 (2012). https://doi.org/10.1038/cmi.2012.1

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