A Human Dectin-2 Deficiency Associated With Invasive Aspergillosis. (18th March 2021)

• Record Type: Journal Article
• Authors: Griffiths, James S; White, P Lewis; Czubala, Magdalena A; Simonazzi, Elena; Bruno, Mariolina; Thompson, Aiysha; Rizkallah, Pierre J; Gurney, Mark; da Fonseca, Diogo M; Naglik, Julian R; Ingram, Wendy; Wilson, Keith; van de Veerdonk, Frank L; Barnes, Rosemary; Taylor, Philip R; Orr, Selinda J
• Is Part Of: Journal of infectious diseases. Volume 224:Number 7(2021)
• Page Start: 1219
• Page End: 1224
• Publication Date: 2021-03-18
• Subjects: Dectin-2 -- CLR -- Aspergillus -- Candida -- fungal immunology -- host–pathogen interactions -- innate immunity -- inflammation; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiab145
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Immunocompromised patients are highly susceptible to invasive aspergillosis. Herein, we identified a homozygous deletion mutation (507 del C) resulting in a frameshift (N170I) and early stop codon in the fungal binding Dectin-2 receptor, in an immunocompromised patient. The mutated form of Dectin-2 was weakly expressed, did not form clusters at/near the cell surface and was functionally defective. Peripheral blood mononuclear cells from this patient were unable to mount a cytokine (tumor necrosis factor, interleukin 6) response to Aspergillus fumigatus, and this first identified Dectin-2–deficient patient died of complications of invasive aspergillosis. Abstract : We identified a Dectin-2 N170I mutation in an immunocompromised patient who died of complications of invasive aspergillosis. This mutation results in an early stop codon and poor receptor expression and renders Dectin-2 functionally defective.