Unravelling fungal immunity through primary immune deficiencies

Abstract

Fungal infections affect individuals with an impaired immune system and are on the increase, often with serious consequences. Recent studies in patients with primary immune deficiencies (PIDs) have led to important breakthroughs in our understanding of the different, mutually exclusive pathways underlying immunity to mucocutaneous as opposed to invasive fungal infections. Patients with defects affecting segments of innate (dectin-1, CARD9, IL12RB1) or adaptive immunity (interleukin (IL)17-F, IL-17 receptor, STAT1, STAT3, antibodies to Th-17 cytokines) that disrupt the Th-17 pathway, are unable to clear superficial Candida or Dermatophyte infections and suffer with chronic mucocutaneous candidiasis (CMC). Patients with defects affecting phagocyte function (oxidative killing, neutropenia) or a severely impaired immune system are at risk of developing invasive, often fatal fungal disease with Aspergillus, Candida, Cryptococcai and other fungi. PIDs are hugely beneficial in promoting our knowledge of fungal immunity and provide important contributions toward evidence-based diagnosis and improved patient care.