From Mendel to mycoses: Immuno-genomic warfare at the human-fungus interface

Area of Science:

• Immunology
• Mycology
• Genetics

Background:

• Fungi typically cause severe disease when host immunity is compromised.
• In rare instances, severe fungal infections occur without obvious immune defects, suggesting underlying causes.
• These causes can include genetic immunodeficiencies or autoantibodies against cytokines.

Purpose of the Study:

• To review the genetic and autoantibody-driven mechanisms underlying susceptibility to severe fungal diseases.
• To explore how studying inborn errors of immunity marked by fungal disease (IEI-FD) can inform our understanding of fungal syndromes.
• To lay the groundwork for developing precision therapies for fungal infections.

Main Methods:

• Literature review of genetic immunodeficiencies and anti-cytokine autoantibodies associated with fungal infections.
• Analysis of case studies presenting with severe fungal disease in the absence of apparent immune compromise.
• Synthesis of findings to establish a framework for understanding IEI-FD.

Main Results:

• Identified genetic immunodeficiencies and anti-cytokine autoantibodies as key factors in rare severe fungal infections.
• Demonstrated variability in onset, severity, and associated infections among individuals with genetic immunodeficiencies.
• Highlighted the potential for IEI-FD to serve as models for deciphering fungal disease pathogenesis.

Conclusions:

• Human genetics and autoantibodies play critical roles in susceptibility to severe fungal infections.
• Understanding IEI-FD provides a valuable framework for mechanistic insights into fungal syndromes.
• This knowledge can potentially lead to targeted, precision-based therapeutic strategies for mycoses.