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Candida albicans morphogenesis and host defence: discriminating invasion from colonization

Nature Reviews Microbiology volume 10, pages 112–122 (2012)Cite this article

Subjects

Key Points

  • Candida albicans is the most common fungal pathogen of humans, and also colonizes the skin and mucosal surfaces of most healthy individuals. Little was known about the mechanisms by which the mucosal immune response tolerates colonizing C. albicans yeast cells but reacts strongly when hyphae invade tissue.

  • C. albicans yeast cells and hyphae differ in their morphological properties, and this has important consequences for their recognition by mucosal immune cells.

  • Different mechanisms, in epithelial cells on the one hand and in immune cells on the other, are important for recognizing fungal invasion of the mucosa.

  • The germination of hyphae and increased fungal loads are recognized by epithelial cells, which then release pro-inflammatory cytokines and chemokines though specific kinase-dependent pathways.

  • Tissue macrophages recognize C. albicans hyphae through inflammasome activation mediated by a dectin 1-dependent pathway. In turn, this results in processing of pro-interleukin-1β and induction of T helper 17-type responses.

  • These mechanisms provide a conceptual framework for our understanding of tolerance to colonization versus immune defence against invasion by C. albicans and probably also by other microorganisms.

Abstract

Candida albicans is a common fungal pathogen of humans that colonizes the skin and mucosal surfaces of most healthy individuals. Until recently, little was known about the mechanisms by which mucosal antifungal defences tolerate colonizing C. albicans but react strongly when hyphae of the same microorganism attempt to invade tissue. In this Review, we describe the properties of yeast cells and hyphae that are relevant to their interaction with the host, and the immunological mechanisms that differentially recognize colonizing versus invading C. albicans.

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Figure 1: Candida albicans tissue invasion.
Figure 2: Structure of the Candida albicans cell wall.
Figure 3: Different stimuli promote the formation of subtly different Candida albicans hyphae.
Figure 4: The main pattern recognition receptors involved in recognizing Candida albicans.
Figure 5: Colonization versus invasion.

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Acknowledgements

N.A.R.G. and A.J.P.B. are supported by the UK Wellcome Trust (grant 080088), the European Commission (through the ALLFUN project; the FINSysB project grant PITN-GA-2008-214004; and the STRIFE project grant ERC-2009-AdG-249793) and the UK Biotechnology and Biological Sciences Research Council (grant BB/F00513X/1). M.G.N. was supported by a Vici grant from the Netherlands Organization for Scientific Research (NWO). F.L.v.d.V. was supported by a Veni grant from NWO.

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Authors and Affiliations

  1. Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK

    Neil A. R. Gow & Alistair J. P. Brown

  2. Department of Medicine and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University, Nijmegen Medical Center, Nijmegen, 6500HB, The Netherlands

    Frank L. van de Veerdonk & Mihai G. Netea

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Correspondence to Mihai G. Netea.

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Glossary

Pseudohyphae

Cells produced by a series of synchronous budding events in which each daughter cell remains attached to its mother cell, thus forming a chain of elongated yeast cells with obvious constrictions at the septal junctions.

Candidiasis

A mucosal fungal infection that can be caused by any of the pathogenic Candida species, of which Candida albicans is the most common.

Adhesins

Cell surface glycoproteins in the fungal cell wall that facilitate microbial adhesion or adherence to other cells or to an inanimate surface; virulence factors.

Invasins

Proteins that are produced by microorganisms to promote microbial penetration into mammalian cells.

Bud scars

Scars located on the surface of the mother cell, representing the remnants of the septum formed between mother and daughter cells during cell division.

Muramyl dipeptide

The minimal structural unit of peptidoglycan in Gram-positive bacteria that is recognized by the intracellular receptor NOD2 (nucleotide-binding oligomerization domain-containing 2).

Cyclin

A family of proteins for which expression is normally periodic within the cell cycle and which control the progression of cells through the cell cycle by activating cyclin-dependent kinases.

Septins

Evolutionarily conserved proteins that have essential functions in bud evagination and cytokinesis, and more subtle roles throughout the cell cycle.

Chlamydospores

Thick-walled spores that are produced by Candida albicans on carbohydrate-rich media in vivo. The presence of chlamydospores in human tissues has yet to be firmly established.

Genotoxic

Pertaining to a substance: able to cause mutations by damaging DNA.

Macrophages

White blood cells produced by the differentiation of monocytes in tissues. Monocytes and macrophages are phagocytes and are important for host defence against Candida albicans infection.

Zymosan

A cell wall preparation that is obtained from the yeast Saccharomyces cerevisiae and comprises a protein–carbohydrate complex rich in β-1,3-glucan.

Myeloid cells

A class of important innate immune cells that are derived from bone marrow and consist of monocytic populations (monocytes and their precursors) and granulocytic populations (granulocytes and their precursors).

T helper 17 cell

(TH17 cell). A newly discovered subset of TH cells that produce interleukin-17 (IL-17), IL-21 and IL-22. These are developmentally distinct from TH1 and TH2 cells and are thought to have a protective role in fungal infection.

Neutrophils

Phagocytic cells that are one of the first inflammatory cell types to migrate to the site of inflammation.

Defensins

A group of small antimicrobial peptides that have direct activity against microorganims.

Inflammasome

A protein platform that triggers activation of inflammatory caspases, which process pro-interleukin-1β.

IL-1β

(Interleukin-1β). A polypeptide that is produced after infection, injury or antigenic challenge and is highly pro-inflammatory. IL-1β is primarily produced by macrophages through a pathway that is tightly regulated by the inflammasome.

T helper 1-type

(TH1-type). A response characterized by the TH1-type cytokine, interferon-γ.

E-cadherin

One of the cadherin proteins, which are a class of type-1 transmembrane protein that plays an important part in cell-to cell adhesion in mammalian tissues.

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Gow, N., van de Veerdonk, F., Brown, A. et al. Candida albicans morphogenesis and host defence: discriminating invasion from colonization. Nat Rev Microbiol 10, 112–122 (2012). https://doi.org/10.1038/nrmicro2711

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