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Updated: Sep 4, 2025
Live Imaging of Antifungal Activity by Human Primary Neutrophils and Monocytes in Response to A. fumigatus
Published on: April 19, 2017
Main human inborn errors of immunity leading to fungal infections
Cristina Cifaldi1, Giorgiana M Ursu2, Irene D'Alba3
1Academic Department of Paediatrics, Immune and Infectious Diseases Division, Research Unit of Primary Immunodeficiencies, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Background:
The host's 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 can develop mild superficial to life-threatening invasive infections. In the last years, thanks to next-generation sequencing, 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 strikes healthy subjects is responsible for the chronic mucocutaneous candidiasis that is one of the principal clinical manifestations occurring in several rare primary immunodeficiencies associated with an inborn error of interleukin-17 (IL-17) immunity.
Objective:
This review aimed to provide an overview of chronic mucocutaneous candidiasis-derived genetic defects, including IL17 deficiencies (IL17A, IL17F, IL17RA, IL17RC), STAT1 gain-of-function deficiency, STAT3 hyper-IgE syndrome, 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 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 a description of therapeutic options.
Implications:
This narrative review will help clinician to identify the correct management of patients based on molecular and cellular findings underlying pathogenic mechanisms of different inborn errors of immunity. Moreover, enabling clinicians to achieve the genetic diagnosis will be useful to offer genetic counselling intra- and inter-family and to ensure a personalised treatment of patients.
Insights
Genetic defects in interleukin-17 (IL-17) immunity and other pathways cause chronic mucocutaneous candidiasis. Understanding these inborn errors of immunity aids in diagnosis and personalized patient treatment.
Area of Science:
- Immunology
- Genetics
- Infectious Diseases
Background:
- Host genetic factors influence susceptibility to fungal infections, with primary immunodeficiencies leading to severe disease.
- Chronic mucocutaneous candidiasis is a key manifestation of inborn errors of interleukin-17 (IL-17) immunity.
- Next-generation sequencing has identified novel genetic variants impacting fungal infection defense.
Purpose of the Study:
- To review genetic defects causing chronic mucocutaneous candidiasis.
- To cover IL-17 deficiencies (IL17A, IL17F, IL17RA, IL17RC), STAT1 gain-of-function, STAT3 hyper-IgE syndrome, and CARD9 deficiency.
- To update knowledge on the genetic and cellular mechanisms of fungal infections.
Main Methods:
- A narrative review was conducted.
- Literature search performed in PubMed for relevant articles, commentaries, and reviews.
- Focus on updated information regarding mechanisms, clinical features, and therapies.
Main Results:
- Detailed description of genetic and cellular mechanisms underlying fungal infections.
- Focus on IL-17-mediated responses in chronic mucocutaneous candidiasis.
- Report on clinical manifestations and therapeutic strategies.
Conclusions:
- This review aids clinicians in managing patients with inborn errors of immunity based on molecular and cellular findings.
- Facilitates genetic diagnosis, counseling, and personalized treatment strategies.
- Improves understanding of pathogenic mechanisms for better patient care.
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