Polymorphisms in Toll-like receptor genes and susceptibility to infections in allogeneic stem cell transplantation
Open accessAbstract
Objective Discovery of genetic variations in the genes encoding for Toll-like receptors (TLRs) has highlighted a potential link between genomic variation of the host and susceptibility to infections.Materials and methods We investigated the association between polymorphisms in the TLR2, TLR4, and TLR9 genes in recipients of allogeneic hematopoietic stem cell transplant and susceptibility to infections caused by cytomegalovirus and filamentous fungi.Results A significant association was observed between the presence of the T-1237C polymorphism (TLR9) and susceptibility to viral pneumonia (p=0.04; odds ratio [OR]: 1.73). For fungi, a significant association was observed between the presence of the cosegregating Asp299Gly/Thr399Ile polymorphisms (TLR4) and fungal colonization (p=0.003; OR: 10.6). However, susceptibility to fungal infections, predominantly fungal pneumonia, was instead significantly decreased in the presence of the same polymorphisms (p=0.03; OR: 0.23).Conclusion Thus, fungal colonization may not predict susceptibility to infection in the presence of these single nucleotide polymorphisms. The finding that defective viral but not fungal sensing may predict susceptibility to infection highlights the divergent function of TLRs in the pathogenesis of opportunistic infections.
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Numerous single-nucleotide polymorphisms within human Toll-like receptors and C-type lectin receptors have been identified as risk factors for fungal disease.
“Numerous single-nucleotide polymorphisms (SNPs) within human TLRs (TLR1 [11], TLR4 [12–15], TLR6 [11], among others) and CLRs (Dectin-1—in particular the Y238X SNP [16–18]; DC-SIGN, mannose receptor and mannose-binding lectin [19–22]) have been identified as risk factors for fungal disease.”
From Race and ethnicity: Risk factors for fungal infections? (2023) · cites this paper as [13]
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Self-citation
- Authors
- Carvalho, A., Cunha, C., Carotti, A., Aloisi, T., Guarrera, O., Di Ianni, M., Falzetti, F., Bistoni, F., Aversa, F., Pitzurra, L., Rodrigues, F., & Romani, L.
- Affiliations
- University of Perugia (IT)
- University of Minho (PT)
- Corresponding author
- Carvalho, Agostinho
- ORCID
- Venue
- Experimental Hematology
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 37
- Issue
- 9
- Pages
- 1022-1029
- ISSN
- 0301-472X (ISSN-L)
- OpenAlex
- W2031814949
- Cited by
- 104
- References
- 60
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 3 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 6 · 2016: 9 · 2015: 6 · 2014: 10 · 2013: 7 · 2012: 8
- FWCI
- 5.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Experimental Hematology (publishedVersion)
- PubMed (publishedVersion)
- RepositóriUM (Universidade do Minho) (submittedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Keywords
- Toll-like receptors, TLR2, TLR4, TLR9, single nucleotide polymorphisms, allogeneic hematopoietic stem cell transplantation, infection susceptibility, cytomegalovirus infection, fungal infection, fungal pneumonia, viral pneumonia, fungal colonization, opportunistic infections
- MeSH terms
- Adult, Cytomegalovirus Infections, Cytomegalovirus, Female, Humans, Infections, Male, Middle Aged, Mycoses, Retrospective Studies, Transplantation, Homologous, Hematologic Neoplasms, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Stem Cell Transplantation, Toll-Like Receptor 2, Toll-Like Receptor 4, Toll-Like Receptor 9
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