From rare disorders of immunity to common determinants of infection: Following the mechanistic thread

The immense interindividual clinical variability during any infection is a long-standing enigma. Inborn errors of IFN-γ and IFN-α/β immunity underlying rare infections with weakly virulent mycobacteria and seasonal influenza virus have inspired studies of two common infections: tuberculosis and COVI...

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Bibliographic Details
Published in:Cell 2022-08, Vol.185 (17), p.3086-3103
Main Authors: Casanova, Jean-Laurent, Abel, Laurent
Format: Article
Language:English
Subjects:
COVID-19
Humans
Interferon-alpha
Interferon-beta
Interferon-gamma
Mycobacterium
Tuberculosis
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Summary:The immense interindividual clinical variability during any infection is a long-standing enigma. Inborn errors of IFN-γ and IFN-α/β immunity underlying rare infections with weakly virulent mycobacteria and seasonal influenza virus have inspired studies of two common infections: tuberculosis and COVID-19. A TYK2 genotype impairing IFN-γ production accounts for about 1% of tuberculosis cases, and autoantibodies neutralizing IFN-α/β account for about 15% of critical COVID-19 cases. The discovery of inborn errors and mechanisms underlying rare infections drove the identification of common monogenic or autoimmune determinants of related common infections. This “rare-to-common” genetic and mechanistic approach to infectious diseases may be of heuristic value. Inborn errors associated with rare susceptibility to weakly virulent agents illuminate fundamental immunopathological mechanisms of disease.
ISSN:0092-8674
1097-4172
1097-4172
DOI:10.1016/j.cell.2022.07.004