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Of Mycelium and Men: Inherent Human Susceptibility to Fungal Diseases

Donald C Vinh1,2,3

  • 1Division of Infectious Diseases (Department of Medicine, McGill University Health Centre), Montreal, QC H4A 3J1, Canada.

Pathogens (Basel, Switzerland)
|March 29, 2023
PubMed

Insights

Inborn errors of immunity (IEI) and autoantibodies explain previously mysterious fungal infections in individuals without clear risk factors. Understanding these immune system defects reveals key pathways of human susceptibility to mycoses.

Area of Science:

  • Immunology
  • Medical Mycology
  • Genetics

Background:

  • Fungal infections (mycoses) can occur in individuals without apparent risk factors, posing diagnostic challenges.
  • Historically, some severe fungal diseases lacked clear explanations for host susceptibility.
  • The field of inborn errors of immunity (IEI) has begun to elucidate these previously enigmatic cases.

Purpose of the Study:

  • To provide a comprehensive update on inborn errors of immunity (IEI) predisposing to fungal diseases.
  • To review the role of naturally occurring autoantibodies against cytokines in fungal susceptibility.
  • To highlight the immunologic dissection of previously unexplained mycoses.

Main Methods:

  • Review of existing literature on IEI and fungal infections.
  • Analysis of genetic and immunologic mechanisms underlying susceptibility.
  • Identification of autoantibodies targeting cytokines that mimic IEI phenotypes.

Main Results:

  • IEI, including single-gene disorders, explains a subset of severe fungal infections.
  • Autoantibodies to cytokines can phenocopy IEI, leading to increased susceptibility to mycoses.
  • Immunologic dissection has identified key pathways mediating susceptibility to fungal infections.

Conclusions:

  • IEI and autoantibodies are critical factors in understanding non-iatrogenic fungal diseases.
  • These discoveries provide a framework for diagnosing and potentially treating severe fungal infections.
  • Further research into host-pathogen interactions in the context of immune defects is warranted.
Keywords:
fungiinborn errors of immunityinvasive fungal diseasemycosesprimary immunodeficiencysuperficial fungal disease

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