Polymorphisms in Toll-like receptor genes and susceptibility to infections in allogeneic stem cell transplantation

Carvalho, Agostinho; Cunha, Cristina; Carotti, Alessandra; Aloisi, Teresa; Guarrera, Ornella; Di Ianni, Mauro; Falzetti, Franca; Bistoni, Francesco; Aversa, Franco; Pitzurra, Lucia; Rodrigues, Fernando; Romani, Luigina

doi:10.1016/j.exphem.2009.06.004

« Previous Next »Experimental Hematology
Volume 37, Issue 9 , Pages 1022-1029, September 2009

Polymorphisms in Toll-like receptor genes and susceptibility to infections in allogeneic stem cell transplantation

Agostinho Carvalho
- Microbiology, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
- Offprint requests to: Agostinho Carvalho, Ph.D., Department of Experimental Medicine and Biochemical Sciences and Ospedale Santa Maria della Misericordia, Microbiology Section, Perugia 06123, Italy
Cristina Cunha
- Microbiology, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
Alessandra Carotti
- Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
Teresa Aloisi
- Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
Ornella Guarrera
- Microbiology, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
Mauro Di Ianni
- Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
Franca Falzetti
- Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
Francesco Bistoni
- Microbiology, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
Franco Aversa
- Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
Lucia Pitzurra
- Microbiology, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
Fernando Rodrigues
- Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal
Luigina Romani
- Microbiology, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy

Received 5 May 2008; received in revised form 29 April 2009; accepted 9 June 2009. published online 18 June 2009.

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.