Main human inborn errors of immunity leading to fungal infections

Clin Microbiol Infect. 2022 Jul 18;S1198-743X(22)00346-9. doi: 10.1016/j.cmi.2022.06.031. Online ahead of print.


Background: The host molecular and genetic features are essential in providing susceptibility to a broad spectrum of fungal infections; most of these do not cause disease in healthy individuals because of mutual benefits with opportunistic fungi besides the host's capacity to control the infections. In contrast, patients with primary immunodeficiency (PID) can develop mild superficial to life-threatening invasive infections. In the last years, thanks to next-generation sequencing (NGS), several inborn-error variants have been discovered in genes encoding protein acting against fungal infections, contributing to better defining the role of innate and adaptive immunity cooperation during infection resolution. Candida fungal infection, that sometimes-striking healthy subjects, is responsible for the chronic mucocutaneous candidiasis (CMC) that is one of the principal clinical manifestations occurring in several rare PIDs associated with an inborn error of IL17-immunity.

Objective: This review aimed to provide an overview of CMC-derived genetic defects, including IL17-deficiencies (IL17A, IL17F, IL17RA, IL17RC), STAT1 gain-of-function (GOF)- deficiency, STAT3-HIES and CARD9-deficiency.

Sources: We carried out detailed research work to identify interesting articles, commentaries, and reviews in the PubMed literature to ensure a correct and updated for this narrative review.

Content: We propose an in-depth description and an update of genetic and cellular mechanisms underlying fungal infections, focusing on the IL17-mediated response, a report of clinical manifestations and describe therapeutic options.

Implication: This narrative review will help clinician to identify the correct management of patients based on molecular and cellular findings underlying pathogenic mechanisms of different IEIs. Moreover achieve the genetic diagnosis will be useful to offer genetic counselling intra- and inter-family and to ensure a personalized treatment of patients.

Keywords: Chronic Mucocutaneous Candidiasis (CMC); Fungal Infections; Inborn Errors of Immunity (IEI); Interleukin-17 immunity; Primary immunodeficiencies (PID).

Publication types

  • Review