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TitleDectin-1 Y238X polymorphism associates with susceptibility to invasive aspergillosis in hematopoietic transplantation through impairment of both recipient : and donor-dependent mechanisms of antifungal immunity
Author(s)Cunha, Cristina
Ianni, Mauro Di
Bozza, Silvia
Giovannini, Gloria
Zagarella, Silvia
Zelante, Teresa
Angelo, Carmen de
Pierini, Antonio
Pitzurra, Lucia
Falzetti, Franca
Carotti, Alessandra
Perruccio, Katia
Latgé, Jean Paul
Rodrigues, Fernando
Velardi, Andrea
Aversa, Franco
Romani, Luigina
Carvalho, Agostinho
Issue date2010
PublisherOxford University Press
JournalMedical Mycology
Abstract(s)The C-type lectin receptor Dectin-1 plays a pivotal role in antifungal immunity. In this study, the recently characterized human DECTIN1 Y238X early stop codon polymorphism leading to diminished Dectin-1 receptor activity was studied in relation to invasive aspergillosis susceptibility and severity in patients receiving hematopoietic stem cell transplantation. We found that the presence of the DECTIN1 Y238X polymorphism in either donors or recipients of hematopoietic stem cell transplantation increased susceptibility to aspergillosis, with the risk being highest when the polymorphism was present simultaneously in both donors and recipients (adjusted hazard ratio = 3.9; P = .005). Functionally, the Y238X polymorphism impaired the production of interferon-? and interleukin-10 (IL-10), in addition to IL-1ß, IL-6, and IL-17A, by human peripheral mononuclear cells and Dectin-1 on human epithelial cells contributed to fungal recognition. Mechanistically, studies on preclinical models of infection in intact or bone marrow-transplanted Dectin-1 knockout mice revealed that protection from infection requires a distinct, yet complementary, role of both donor and recipient Dectin-1. This study discloses Dectin-1 deficiency as a novel susceptibility factor for aspergillosis in high-risk patients and identifies a previously unsuspected role for Dectin-1 in antifungal immunity that is the ability to control both resistance and tolerance to the fungus contingent on hematopoietic/nonhematopoietic compartmentalization.
Publisher version
AccessOpen access
Appears in Collections:ICVS - Artigos em revistas internacionais / Papers in international journals

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