Author | Marques, Carolinne de Sales | |
Author | Souza, Vânia N. Brito de | |
Author | Guerreiro, Luana Tatiana Albuquerque | |
Author | Martins, João H. | |
Author | Amaral, Evaldo P. | |
Author | Cardoso, Cynthia C. | |
Author | Batista, Ida Maria Foschiani Dias | |
Author | Silva, Weber Laurentino da | |
Author | Nery, José Augusto C. | |
Author | Medeiros, Priscila | |
Author | Gigliotti, Patricia | |
Author | Campanelli, Ana Paula | |
Author | Virmond, Marcos | |
Author | Sarno, Euzenir Nunes | |
Author | Mira, Marcelo T. | |
Author | Lana, Francisco C. F. | |
Author | Caffarena, Ernesto Raul | |
Author | Pacheco, Antonio G. | |
Author | Pereira, Ana Carla | |
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 (TLR1) N248S single nucleotide polymorphism is associated with leprosy risk and regulates immune activation during mycobacterial infection. Journal of Infectious Diseases, v.208, n.1, p.120-9, Jul. 2013. | pt_BR |
ISSN | 0022-1899 | |
URI | https://www.arca.fiocruz.br/handle/icict/12577 | |
Language | eng | pt_BR |
Publisher | Oxford University Press | pt_BR |
Rights | open access | |
Subject in Portuguese | Fator de Necrose Tumoral | pt_BR |
Subject in Portuguese | Citocina | pt_BR |
Subject in Portuguese | Hanseníase | pt_BR |
Subject in Portuguese | Polimorfismo de Nucleotídeo Único | pt_BR |
Title | Toll-like receptor 1 (TLR1) N248S single nucleotide polymorphism is associated with leprosy risk and regulates immune activation during mycobacterial infection | pt_BR |
Type | Article | |
Abstract | TLR1 variants N248S and I602S have been described associated with leprosy,
but different results were found. Here, we performed both a case-control and
family-based studies followed by replication in two case-control samples from
Brazil, enrolling 3,162 individuals. Results indicated risk association between
TLR1 248S and leprosy in case-control (OR SS genotype= 1.81, p=0.004) and
familial study (z=2.02, p=0.05). This association was consistently replicated in
other populations (ORCombined=1.51, p-value<0.001), corroborating 248S as a
susceptibility factor for leprosy. Additionally, we demonstrated that PBMCs
carrying 248S produce lower log(TNF/IL-10) when stimulated with M. leprae,
but not with LPS or PAM3cysK4. The same effect was observed after infection of
PBMCs with BCG Moreau, but not other strains. Finally, molecular dynamics
simulations indicated that 248S-TLR1 structure is different than 248N-TLR1.
Our results suggest that TLR1 248S is associated with leprosy risk, consistent
with its hypo-immune regulatory function. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Instituto Lauro de Souza Lima. Bauru, SP, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Programa de Computação Científica (PROCC). Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Departamento de Enfermagem Materno-Infantil e Saúde Pública. Belo Horizonte, MG, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Departamento de Genética. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Instituto Lauro de Souza Lima. Bauru, SP, Brasil. | pt_BR |
Affilliation | Instituto Lauro de Souza Lima. Bauru, SP, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Instituto Lauro de Souza Lima. Bauru, SP, Brasil. | pt_BR |
Affilliation | Instituto Lauro de Souza Lima. Bauru, SP, Brasil. | pt_BR |
Affilliation | Universidade de São Paulo. Escola de Odontologia de Bauru. Departamento de Ciências Biológicas. Bauru, SP, Brasil. | pt_BR |
Affilliation | Instituto Lauro de Souza Lima. Bauru, SP, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Católica do Paraná. Escola de Medicina. Programa de Pós-Graduação em Ciências da Saúde. Curitiba, PR, Brasil. | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Departamento de Enfermagem Materno-Infantil e Saúde Pública. Belo Horizonte, MG, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Programa de Computação Científica (PROCC). Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Programa de Computação Científica (PROCC). Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Instituto Lauro de Souza Lima. Bauru, SP, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | IL-10 | pt_BR |
Subject | N248S | pt_BR |
Subject | SNPs | pt_BR |
Subject | TLR1 | pt_BR |
Subject | TNF | pt_BR |
Subject | Cytokine | pt_BR |
Subject | Leprosy | pt_BR |
e-ISSN | 1537-6613 | |