title: Polymorphisms in Toll-like receptor genes and susceptibility to infections in allogeneic stem cell transplantation.
abstract: 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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Microbiology, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy. aacarvalho2008@gmail.com
authors.forename: Agostinho
authors.initials: A
authors.lastname: Carvalho
authors.forename: Cristina
authors.initials: C
authors.lastname: Cunha
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carotti
authors.forename: Teresa
authors.initials: T
authors.lastname: Aloisi
authors.forename: Ornella
authors.initials: O
authors.lastname: Guarrera
authors.forename: Mauro
authors.initials: M
authors.lastname: Di Ianni
authors.forename: Franca
authors.initials: F
authors.lastname: Falzetti
authors.forename: Francesco
authors.initials: F
authors.lastname: Bistoni
authors.forename: Franco
authors.initials: F
authors.lastname: Aversa
authors.forename: Lucia
authors.initials: L
authors.lastname: Pitzurra
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodrigues
authors.forename: Luigina
authors.initials: L
authors.lastname: Romani
mesh_terms: D000328:Adult; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D019337:Hematologic Neoplasms / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000628:therapy / Q000821:virology; D006801:Humans; D007239:Infections / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000235:genetics* / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9