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.
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.
Authors: Rohina Rubicz; Charles T Leach; Ellen Kraig; Nikhil V Dhurandhar; Ravindranath Duggirala; John Blangero; Robert Yolken; Harald H H Göring Journal: Hum Hered Date: 2011-10-11 Impact factor: 0.444
Authors: A Carvalho; C Cunha; A J Almeida; N S Osório; M Saraiva; M Teixeira-Coelho; S Pedreiro; E Torrado; N Domingues; A G Gomes-Alves; A Marques; J F Lacerda; M G da Silva; M Gomes; A C Pinto; F Torres; P Rendeiro; P Tavares; M Di Ianni; R Medeiros; P Heutink; P M Bracci; L Conde; P Ludovico; J Pedrosa; P Maciel; L Pitzurra; F Aversa; H Marques; A Paiva; C F Skibola; L Romani; A G Castro; F Rodrigues Journal: Genes Immun Date: 2011-08-25 Impact factor: 2.676
Authors: Matthew G Drake; Scott E Evans; Burton F Dickey; Allison D Fryer; David B Jacoby Journal: Am J Respir Cell Mol Biol Date: 2013-06 Impact factor: 6.914