| Author | Marques, Carolinne de Sales | |
| Author | Souza, Vânia Nieto Brito de | |
| Author | Guerreiro, Luana Tatiana Albuquerque | |
| Author | Silva, João Hermínio Martins da | |
| Author | Amaral, Evaldo Pinheiro | |
| Author | Cardoso, Cynthia Chester | |
| Author | Batista, Ida Maria Foschiani Dias | |
| Author | Silva, Weber Laurentino da | |
| Author | Nery, José Augusto da Costa | |
| Author | Medeiros, Priscila | |
| Author | Gomes, Patricia Gigliotti | |
| Author | Campanelli, Ana Paula | |
| Author | Virmond, Marcos da Cunha Lopes | |
| Author | Sarno, Euzenir Nunes | |
| Author | Mira, Marcelo Távora | |
| Author | Lana, Francisco Carlos Félix | |
| Author | Caffarena, Ernesto Raul | |
| Author | Pacheco, Antonio Guilherme Fonseca | |
| Author | Latini, Ana Carla Pereira | |
| Author | Moraes, Milton Ozório | |
| Access date | 2016-01-21T13:14:09Z | |
| Available date | 2016-01-21T13:14:09Z | |
| Document date | 2013 | |
| Citation | MARQUES, Carolinne de Sales et al. Toll-like receptor 1 N248S single-nucleotide polymorphism is associated with leprosy risk and regulates immune activation during mycobacterial infection. The Journal of Infectious Diseases, v. 208, p. 120-129, 1 Jul. 2013. | |
| ISSN | 0022-1899 | |
| URI | https://www.arca.fiocruz.br/handle/icict/12577 | |
| Description | Produção científica Laboratório de Hanseníase. | pt_BR |
| Language | eng | en_US |
| Publisher | Oxford University Press | |
| Rights | open access | |
| Title | Toll-like receptor 1 N248S single-nucleotide polymorphism is associated with leprosy risk and regulates immune activation during mycobacterial infection | en_US |
| Type | Article | |
| Abstract | Conflicting findings about the association between leprosy and TLR1 variants N248S and I602S have been reported. Here, we performed case-control and family based studies, followed by replication in 2 case-control populations from Brazil, involving 3162 individuals. Results indicated an association between TLR1 248S and leprosy in the case-control study (SS genotype odds ratio [OR], 1.81; P = .004) and the family based study (z = 2.02; P = .05). This association was consistently replicated in other populations (combined OR, 1.51; P < .001), corroborating the finding that 248S is a susceptibility factor for leprosy. Additionally, we demonstrated that peripheral blood mononuclear cells (PBMCs) carrying 248S produce a lower tumor necrosis factor/interleukin-10 ratio when stimulated with Mycobacterium leprae but not with lipopolysaccharide or PAM₃cysK₄. The same effect was observed after infection of PBMCs with the Moreau strain of bacillus Calmette-Guerin but not after infection with other strains. Finally, molecular dynamics simulations indicated that the Toll-like receptor 1 structure containing 248S amino acid is different from the structure containing 248N. Our results suggest that TLR₁ 248S is associated with an increased risk for leprosy, consistent with its hypoimmune regulatory function. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Instituto Lauro de Souza Lima. Bauru, SP, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Presidência. Programa de Computação Científica. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Universidade Federal de Minas Gerais. Escola de Enfermagem. Departamento de Enfermagem Materno-Infantil e Saúde Pública. Belo Horizonte, MG, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Departamento de Genética. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Instituto Lauro de Souza Lima. Bauru, SP, Brasil. | |
| Affilliation | Instituto Lauro de Souza Lima. Bauru, SP, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Instituto Lauro de Souza Lima. Bauru, SP, Brasil. | |
| Affilliation | Instituto Lauro de Souza Lima. Bauru, SP, Brasil. | |
| Affilliation | Universidade de São Paulo. Escola de Odontologia de Bauru. Departamento de Ciências Biológicas. Bauru, SP, Brasil. | |
| Affilliation | Instituto Lauro de Souza Lima. Bauru, SP, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Universidade Católica do Paraná. Escola de Medicina. Programa de Pós-Graduação em Ciências da Saúde. Curitiba, PR, Brasil. | |
| Affilliation | Universidade Federal de Minas Gerais. Escola de Enfermagem. Departamento de Enfermagem Materno-Infantil e Saúde Pública. Belo Horizonte, MG, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Presidência. Programa de Computação Científica. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Presidência. Programa de Computação Científica. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Instituto Lauro de Souza Lima. Bauru, SP, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | |
| Subject | TLR1 | en_US |
| Subject | Leprosy | en_US |
| Subject | SNPs | en_US |
| Subject | N248S | en_US |
| Subject | TNF | en_US |
| Subject | IL-10 | en_US |
| Subject | Cytokine | en_US |
| e-ISSN | 1537-6613 | |
