Dectin-1 Y238X polymorphism associates with susceptibility to invasive aspergillosis in hematopoietic transplantation through impairment of both recipient- and donor-dependent mechanisms of antifungal immunity.
Summary of "Dectin-1 Y238X polymorphism associates with susceptibility to invasive aspergillosis in hematopoietic transplantation through impairment of both recipient- and donor-dependent mechanisms of antifungal immunity."
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 transplant (HSCT). We found that the presence of the DECTIN1 Y238X polymorphism in either donors or recipients of HSCT 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=0.005). Functionally, the Y238X polymorphism impaired the production of IFN-gamma and IL-10, in addition to IL-1beta, 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 KO 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 upon hematopoietic/nonhematopoietic compartmentalization.
Affiliation
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy;
Journal Details
This article was published in the following journal.
Name: Blood
ISSN: 1528-0020
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20807886
- DOI: http://dx.doi.org/10.1182/blood-2010-04-279307
Medical and Biotech [MESH] Definitions
Invasive Pulmonary Aspergillosis
Lung infections with the invasive forms of ASPERGILLUS, usually after surgery, transplantation, prolonged NEUTROPENIA or treatment with high-doses of CORTICOSTEROIDS. Invasive pulmonary aspergillosis can progress to CHRONIC NECROTIZING PULMONARY ASPERGILLOSIS or hematogenous spread to other organs.
Pulmonary Aspergillosis
Infections of the respiratory tract with fungi of the genus ASPERGILLUS. Infections may result in allergic reaction (ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS), colonization in pulmonary cavities as fungus balls (MYCETOMA), or lead to invasion of the lung parenchyma (INVASIVE PULMONARY ASPERGILLOSIS).
Polymorphism, Genetic
The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.
Radiography, Interventional
Diagnostic and therapeutic procedures that are invasive or surgical in nature, and require the expertise of a specially trained radiologist. In general, they are more invasive than diagnostic imaging but less invasive than major surgery. They often involve catheterization, fluoroscopy, or computed tomography. Some examples include percutaneous transhepatic cholangiography, percutaneous transthoracic biopsy, balloon angioplasty, and arterial embolization.
Surgical Procedures, Minimally Invasive
Procedures that avoid use of open invasive surgery in favor of closed or local surgery. These generally involve use of laparoscopic devices and remote-control manipulation of instruments with indirect observation of the surgical field through an endoscope or similar device. With the reduced trauma associated with minimally invasive surgery, long hospital stays may be reduced with increased rates of short stay or day surgery.
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