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  • Review Article
  • Published:

Immune defence against Candida fungal infections

Nature Reviews Immunology volume 15, pages 630–642 (2015)Cite this article

Subjects

Key Points

  • Candida albicans is the most important fungal pathogen in humans, and it causes both mucosal and systemic fungal infections.

  • Innate immune recognition by pattern recognition receptors (PRRs) is the first step for activation of host defence mechanisms during Candida infections. C-type lectin receptors (CLRs) are the main family of PRRs involved in recognition of Candida species, but Toll-like receptors, NOD-like receptors and RIG-I-like receptors are also involved in the antifungal response.

  • Neutrophils, monocytes and macrophages are the main immune cell populations responsible for host defence against systemic candidiasis, whereas T helper 1 (TH1) cells, TH17 cells and innate lymphoid cells are mainly responsible for protection against Candida infections at mucosal surfaces.

  • C. albicans and components from its cell wall, particularly β-glucans, have the capacity to induce epigenetic reprogramming of innate immune cells, generating a de facto innate immune memory that has been termed 'trained immunity'.

  • Systems biology approaches combining innovative genomic, microbiome and functional data open new possibilities for identifying key mechanisms in the pathophysiology of fungal infections.

  • Future efforts need to combine cutting-edge molecular and cell-biological techniques with translational approaches in order to gain a better understanding of the host immune response to Candida infections and enable the design of novel antifungal strategies.

Abstract

The immune response to Candida species is shaped by the commensal character of the fungus. There is a crucial role for discerning between colonization and invasion at mucosal surfaces, with the antifungal host defence mechanisms used during mucosal or systemic infection with Candida species differing substantially. Here, we describe how innate sensing of fungi by pattern recognition receptors and the interplay of immune cells (both myeloid and lymphoid) with non-immune cells, including platelets and epithelial cells, shapes host immunity to Candida species. Furthermore, we discuss emerging data suggesting that both the innate and adaptive immune systems display memory characteristics after encountering Candida species.

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Figure 1: Recognition of Candida species by innate immune cells.
Figure 2: Interleukin-1β processing during Candida infection.
Figure 3: Effector mechanisms for the clearance of Candida.

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Acknowledgements

M.G.N. was supported by a Vici Grant of the Netherlands Organization for Scientific Research and a European Research Council Consolidator Grant (#310372). F.L.v.d.V. was supported by a Veni Grant of the Netherlands Organization for Scientific Research. The authors thank K. Becker for the help with designing the figures, and they apologize to the colleagues whose work could not be cited owing to space constraints.

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  1. Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, 6525 GA, The Netherlands

    Mihai G. Netea, Leo A. B. Joosten, Jos W. M. van der Meer, Bart-Jan Kullberg & Frank L. van de Veerdonk

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Netea, M., Joosten, L., van der Meer, J. et al. Immune defence against Candida fungal infections. Nat Rev Immunol 15, 630–642 (2015). https://doi.org/10.1038/nri3897

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