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Curr Opin Microbiol. 2017 Dec;40:46-57. doi: 10.1016/j.mib.2017.10.016. Epub 2017 Nov 10.

Inborn errors of immunity underlying fungal diseases in otherwise healthy individuals.

Author information

1
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA.
2
Infectious Disease Susceptibility Program, McGill University Health Centre (MUHC) and Research Institute-MUHC (RI-MUHC), Montreal, Quebec, Canada.
3
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 75015 Paris, EU, France; Paris Descartes University, Imagine Institute, 75015 Paris, EU, France; Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children, 75015 Paris, EU, France; Howard Hughes Medical Institute, New York, NY 10065, USA.
4
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 75015 Paris, EU, France; Paris Descartes University, Imagine Institute, 75015 Paris, EU, France. Electronic address: anne.puel@inserm.fr.

Abstract

It has been estimated that there are at least 1.5 million fungal species, mostly present in the environment, but only a few of these fungi cause human disease. Most fungal diseases are self-healing and benign, but some are chronic or life-threatening. Acquired and inherited defects of immunity, including breaches of mucocutaneous barriers and circulating leukocyte deficiencies, account for most severe modern-day mycoses. Other types of infection typically accompany these fungal infections. More rarely, severe fungal diseases can strike otherwise healthy individuals. Historical reports of fungi causing chronic peripheral infections (e.g. affecting the nails, skin, hair), and invasive diseases (e.g. brain, lungs, liver), in otherwise healthy patients, can be traced back to the mid-20th century. These fungi typically cause endemic, but not epidemic diseases, are more likely to underlie sporadic than familial cases, and only threaten a small proportion of infected individuals. The basis of this 'idiosyncratic' susceptibility has long remained unexplained, but it has recently become apparent that 'idiopathic' fungal diseases, in children, teenagers, and even adults, may be caused by single-gene inborn errors of immunity. The study of these unusual primary immunodeficiencies (PIDs) has led to the identification of molecules and cells playing a crucial role in human host defenses against certain fungi at particular anatomic sites. A picture is emerging of inborn errors of IL-17 immunity selectively underlying chronic mucocutaneous candidiasis, with little inter-individual variability, and of inborn errors of CARD9 immunity underlying various life-threatening invasive fungal diseases, differing between patients.

PMID:
29128761
PMCID:
PMC5733726
DOI:
10.1016/j.mib.2017.10.016
[Indexed for MEDLINE]
Free PMC Article

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