Association between polymorphisms in the genes encoding toll-like receptors and dectin-1 and susceptibility to invasive aspergillosis: a systematic review

Abstract

Invasive aspergillosis is a common fungal infection in immunocompromised individuals. Some studies have shown that tolllike receptor and dectin-1 genetic polymorphisms may alter signaling pathways, thus increasing an individual's susceptibility to invasive aspergillosis. We investigated the pertinent literature to determine whether polymorphisms in the genes encoding tolllike receptors and dectin-1 increase the susceptibility to invasive aspergillosis. This study systematically reviewed the literature using the databases PubMed/PMC, Scopus, and Web of Science using the keywords invasive aspergillosis, polymorphism, Toll-like, and Dectin-1. From the initial search, 415 studies were found and according to our inclusion and exclusion criteria, eight studies were selected. Several studies described single-nucleotide polymorphisms (SNPs) that are associated with a greater susceptibility to invasive aspergillosis. These SNPs were found in the genes that encode toll-like receptors 1, 3, 4, and 5 and the gene that encodes dectin-1; upon activation, both cellular receptors initiate a signaling cascade that can result in the production of cytokines and chemokines. Thus, our literature review uncovered a significant association between polymorphisms in the genes that encode toll-like receptors and dectin-1 and invasive aspergillosis. More studies should be performed to better understand the relationship between toll-like receptor and dectin-1 genetic polymorphisms and invasive aspergillosis susceptibility.

Dectin-1/IL-15 Pathway Affords Protection against Extrapulmonary <i>Aspergillus fumigatus</i> Infection by Regulating Natural Killer Cell Survival

“…Reinforcing this notion, it is interesting to notice that human data about dectin-1 genetic polymorphisms and invasive aspergillosis observed this link in immunosuppressed subjects (as cancer or post organ transplantation patients) [12], albeit they lacked a former history of Aspergillus infections previously to their immunodepression. Because clinical immunosuppression (pharmacological or secondary to infections as by HIV) is not lymphocyte-specific, as other immune cells, as NK cells, or even the expression of immune receptors can be affected either [43][44][45][46], it is likely that these depressive states weaken the pulmonary defenses which facilitate the fungus to transpose the lungs.…”

“…However, considering the key role played by dectin-1 in anti-Aspergillus defense suggested by genetic studies that identified Clec7a polymorphisms as risk factors for developing severe aspergillosis [10][11][12], the receptor may also be critical for host defense in extrapulmonary locations. Since A. fumigatus is potentially invasive, able to cause disseminated disease, dectin-1 might also contribute to host defense in the periphery, yet this is still a poorly explored topic and possible effector mechanisms remain unknown.…”

Incorporating the Detection of Single Nucleotide Polymorphisms Associated With Invasive Aspergillosis Into the Clinic

“…toll like receptors (TLR) or C-type lectin receptors] alter the signalling pathway of the host's innate immune response, but a wide array of genetic variations in other genes encoding innate immunity components have been documented, along with genetic variation in components of the host's adaptive immunity (e.g. Th-17 or IFN-g, Table 1) (van der Velden et al, 2011;Sainz et al, 2012;Lupiañez et al, 2015;Fisher et al, 2017;Cunha et al, 2018;Cunha and Carvalho, 2019).…”

Genetic Susceptibility to Fungal Infections and Links to Human Ancestry

“…A genetic defect in the different types of PRR families makes the host susceptible to fungal infection ( Netea et al, 2012 ). Defect in the CLR Dectin1, encoded by CLEC7A (C-type lectin domain containing 7A) predisposes humans to invasive aspergillosis (IA), chronic mucocutaneous candidiasis (CMC), and recurrent vulvovaginal candidiasis (RVVC) ( Reid et al, 2009 ; Plantinga et al, 2012 ; Cunha et al, 2018 ). The CLEC7A intronic SNPs rs3901533 and rs7309123 are associated with susceptibility to invasive pulmonary aspergillosis (IPA) in patients with hematologic diseases ( Taylor et al, 2007 ; Sainz et al, 2012 ).…”