Year: 2026
Type: article
Abstract: The provocative idea that a process as apparently complex as a lethal infection can be due to a cause as simple as a rare or common germline single-gene lesion has been documented over the last 30 years for a growing number of infections, and such variants have been diagnosed in an even larger number of patients. A monogenic lesion can predispose a healthy person, who has fended off other microbes, to death following infection with a specific microbe that has proved harmless in most other infected individuals. Remarkably, studies of monogenic infections led to the discovery that autoimmunity targeting the same component of host defense, sometimes due to another type of single-gene mutation, can also underlie the same infection. Both types of single-gene lesions are highly pleiotropic, depending on microbial challenges, and incompletely penetrant, depending on age. I discuss here the roots and implications of a monogenic architecture of life-threatening human infectious diseases, in terms of both basic biology and public health.
Source: Journal of Human Immunity
Author: Jean-Laurent Casanova
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: diamond
Funders: Howard Hughes Medical Institute, Fisher Center for Alzheimer's Research Foundation, St. Giles Foundation, Meyer Foundation, JPB Foundation, Rockefeller University, Fondation du Souffle, SCOR Corporate Foundation for Science, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Stavros Niarchos Foundation, National Institutes of Health, Horizon 2020 Framework Programme, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences
Awards: Autosomal dominant OTULIN deficiency and staphylococcal disease, Molecular and cellular basis of epidermodysplasia verruciformis, G250961418, G686524630, G7617908122, G9000093058, G9000122699, G9000162752, G9000217093, G9000261049, Genome-Wide Dissection of Mendelian Susceptibility to Mycobacterial Disease, Developing, Demonstrating, and Disseminating Innovative Programs to Achieve Translational Success
OpenAlex ID: W7141522702