Immunity to Fungi


Fungi are microorganisms that are ubiquitous in the environment. To establish themselves in the host, they employ a broad variety of virulence strategies. Fungi are an important source of morbidity in humans. However, despite millions of species, only about a hundred cause disease, owing to a remarkable collaboration of the innate and adaptive immune systems. In individuals who have immunocompromised cellular immunity, fungi readily cause invasive disease. Our knowledge of how the immune system prevents invasive fungal disease has been greatly aided by the study of acquired or inherited immune defects. However, much remains to be known in order to improve our ability to treat fungal infections, and our ability to control endemic disease in many areas of the world remains limited, warranting more research towards immunomodulatory interventions.

Key Concepts

  • Fungi readily colonise the environment including our skin and mucosal surfaces.
  • Invasive fungal infections largely occur in individuals with impaired immunity, although infections are endemic in many areas of the world in immunocompetent hosts.
  • T cells and neutrophils are essential in preventing invasive fungal disease.
  • In immunocompromised hosts, fungi frequently cause disease by direct invasion, and also indirectly (i.e. through exaggerated host immune responses).
  • Fungal infections are a major cause of morbidity and mortality worldwide.

Keywords: immune system; fungus; humoral immunity; cellular immunity; immunotherapy; humans; immunodeficiency

Figure 1. Interplay of innate and adaptive immunity to fungi. Orange boxes show potential therapeutic interventions. Key: Th, T helper cell; TReg, T regulatory cell; IL, interleukin; TNF, tumour necrosis factor; IFN, interferon; TGF, transforming growth factor; PRR, pattern‐recognition receptor; MBL, mannan‐binding lectin; GM‐CSF, granulocyte–macrophage colony‐stimulating factor; G‐CSF, granulocyte colony‐stimulating factor.


Aliaga S, Clark RH, Laughon M, et al. (2014) Changes in the incidence of candidiasis in neonatal intensive care units. Pediatrics 133 (2): 236–242.

Arnold DE and Heimall JR (2017) A review of chronic granulomatous disease. Advances in Therapy 34 (12): 2543–2557.

von Bernuth H, Picard C, Jin Z, et al. (2008) Pyogenic bacterial infections in humans with MyD88 deficiency. Science 321 (5889): 691–696.

Bourgeois C and Kuchler K (2012) Fungal pathogens – a sweet and sour treat for toll‐like receptors. Frontiers in Cellular and Infection Microbiology 2: 142.

Brown GD, Denning DW, Gow NA, et al. (2012) Hidden killers: human fungal infections. Science Translational Medicine 4 (165): 1–10.

Casadevall A and Pirofski L‐A (2012) Immunoglobulins in defense, pathogenesis, and therapy of fungal diseases. Cell Host & Microbe 11 (5): 447–456.

Conti HR and Gaffen SL (2015) IL‐17‐mediated immunity to the opportunistic fungal pathogen Candida albicans. Journal of Immunology 195 (3): 780–788.

Delsing CE, Gresnigt MS, Leentjens J, et al. (2014) Interferon‐gamma as adjunctive immunotherapy for invasive fungal infections: a case series. BMC Infectious Diseases 14: 166.

Elluru SR, Kaveri SV and Bayry J (2015) The protective role of immunoglobulins in fungal infections and inflammation. Seminars in Immunopathology 37 (2): 187–197.

Feldmesser M and Casadevall A (1997) Effect of serum IgG1 to Cryptococcus neoformans glucuronoxylomannan on murine pulmonary infection. Journal of Immunology 158 (2): 790–799.

Gringhuis SI, Kaptein TM, Wevers BA, et al. (2012) Dectin‐1 is an extracellular pathogen sensor for the induction and processing of IL‐1β via a noncanonical caspase‐8 inflammasome. Nature Immunology 13 (3): 246–254.

Hontelez S, Sanecka A, Netea MG, et al. (2012) Molecular view on PRR cross‐talk in antifungal immunity. Cellular Microbiology 14 (4): 467–474.

Köhler JR, Casadevall A and Perfect J (2014) The spectrum of fungi that infects humans. Cold Spring Harbor Perspectives in Medicine 5 (1): 1–22.

Limper AH, Adenis A, Le T, et al. (2017) Fungal infections in HIV/AIDS. Lancet Infectious Diseases 17 (11): e334–e343.

Lionakis MS, Iliev ID and Hohl TM (2017) Immunity against fungi. JCI Insight 2 (11): 1–17.

Matzaraki V, Gresnigt MS, Jaeger M, et al. (2017) An integrative genomics approach identifies novel pathways that influence candidaemia susceptibility. PLoS One 12 (7): 1–18.

Michalski C, Kan B and Lavoie PM (2017) Antifungal immunological defenses in newborns. Frontiers n Immunology 8: 1–8.

Mignon B, Tabart J, Baldo A, et al. (2008) Immunization and dermatophytes. Current Opinion in Infectious Diseases 21 (2): 134–140.

Netea MG, Joosten LA, van der Meer JW, et al. (2015) Immune defence against Candida fungal infections. Nature Reviews Immunology 15 (10): 630–642.

Pachl J, Svoboda P, Jacobs F, et al. (2006) A randomized, blinded, multicenter trial of lipid‐associated amphotericin B alone versus in combination with an antibody‐based inhibitor of heat shock protein 90 in patients with invasive candidiasis. Clinical Infectious Diseases 42 (10): 1404–1413.

Pandiyan P, Conti HR, Zheng L, et al. (2011) CD4(+)CD25(+)Foxp3(+) regulatory T cells promote Th17 cells in vitro and enhance host resistance in mouse Candida albicans Th17 cell infection model. Immunity 34 (3): 422–434.

Queiroz‐Telles F, Fahal AH, Falci DR, et al. (2017) Neglected endemic mycoses. Lancet Infectious Diseases 7 (11): e367–e377.

Skattum L, van Deuren M, van der Poll T, et al. (2011) Complement deficiency states and associated infections. Molecular Immunology 48 (14): 1643–1655.

Speth C, Rambach G, Würzner R, et al. (2008) Complement and fungal pathogens: an update. Mycoses 51 (6): 477–496.

Sutton CE, Mielke LA and Mills KH (2012) IL‐17‐producing γδ T cells and innate lymphoid cells. European Journal of Immunology 42 (9): 2221–2231.

Swidergall M and Ernst JF (2014) Interplay between Candida albicans and the antimicrobial peptide armory. Eukaryotic Cell 13 (8): 950–957.

Tsoni SV, Kerrigan AM, Marakalala MJ, et al. (2009) Complement C3 plays an essential role in the control of opportunistic fungal infections. Infection and Immunity 77 (9): 3679–3685.

Turvey SE, Durandy A, Fischer A, et al. (2014) The CARD11‐BCL10‐MALT1 (CBM) signalosome complex: stepping into the limelight of human primary immunodeficiency. Journal of Allergy and Clinical Immunology 134 (2): 276–284.

Wang X, van de Veerdonk FL and Netea MG (2016) Basic genetics and immunology of Candida infections. Infectious Disease Clinics of North America 30 (1): 85–102.

Further Reading

Armstrong‐James D, Brown GD, Netea MG, et al. (2017) Immunotherapeutic approaches to treatment of fungal diseases. Lancet Infectious Diseases 17 (12): e393–e402.

Köhler JR, Hube B, Puccia R, et al. (2017) Fungi that infect humans. Microbiology Spectrum 5 (3): 134–140.

Li J, Vinh DC, Casanova JL, et al. (2017) Inborn errors of immunity underlying fungal diseases in otherwise healthy individuals. Current Opinion in Microbiology 40: 46–57.

Lionakis MS and Levitz SM (2017) Host control of fungal infections: lessons from basic studies and human cohorts. Annual Review of Immunology [Epub ahead of print].

Rinaldi MG (2000) Dermatophytosis: epidemiological and microbiological update. Journal of the American Academy of Dermatology 43 (5 Suppl): S120–S124.

Scriven JE, Tenforde MW, Levitz SM, et al. (2017) Modulating host immune responses to fight invasive fungal infections. Current Opinion in Microbiology 40: 95–103.

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Michalski, Christina, Sadarangani, Manish, and Lavoie, Pascal M(Apr 2018) Immunity to Fungi. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000494.pub3]