The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis.

The factors that govern the development of tuberculosis disease are incompletely understood. We hypothesized that some strains of Mycobacterium tuberculosis (M. tuberculosis) are more capable of causing disseminated disease than others and may be associated with polymorphisms in host genes responsib...

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Auteurs principaux: Caws, M, Thwaites, G, Dunstan, S, Hawn, T, Lan, N, Thuong, N, Stepniewska, K, Huyen, M, Bang, N, Loc, T, Gagneux, S, van Soolingen, D, Kremer, K, van der Sande, M, Small, P, Anh, P, Chinh, N, Quy, H, Duyen, N, Tho, D, Hieu, N, Torok, E, Hien, T, Dung, N, Nhu, N, Duy, P, van Vinh Chau, N, Farrar, J
Format: Journal article
Langue:English
Publié: 2008
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author Caws, M
Thwaites, G
Dunstan, S
Hawn, T
Lan, N
Thuong, N
Stepniewska, K
Huyen, M
Bang, N
Loc, T
Gagneux, S
van Soolingen, D
Kremer, K
van der Sande, M
Small, P
Anh, P
Chinh, N
Quy, H
Duyen, N
Tho, D
Hieu, N
Torok, E
Hien, T
Dung, N
Nhu, N
Duy, P
van Vinh Chau, N
Farrar, J
author_facet Caws, M
Thwaites, G
Dunstan, S
Hawn, T
Lan, N
Thuong, N
Stepniewska, K
Huyen, M
Bang, N
Loc, T
Gagneux, S
van Soolingen, D
Kremer, K
van der Sande, M
Small, P
Anh, P
Chinh, N
Quy, H
Duyen, N
Tho, D
Hieu, N
Torok, E
Hien, T
Dung, N
Nhu, N
Duy, P
van Vinh Chau, N
Farrar, J
author_sort Caws, M
collection OXFORD
description The factors that govern the development of tuberculosis disease are incompletely understood. We hypothesized that some strains of Mycobacterium tuberculosis (M. tuberculosis) are more capable of causing disseminated disease than others and may be associated with polymorphisms in host genes responsible for the innate immune response to infection. We compared the host and bacterial genotype in 187 Vietnamese adults with tuberculous meningitis (TBM) and 237 Vietnamese adults with uncomplicated pulmonary tuberculosis. The host genotype of tuberculosis cases was also compared with the genotype of 392 cord blood controls from the same population. Isolates of M. tuberculosis were genotyped by large sequence polymorphisms. The hosts were defined by polymorphisms in genes encoding Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and Toll-like receptor-2 (TLR-2). We found a significant protective association between the Euro-American lineage of M. tuberculosis and pulmonary rather than meningeal tuberculosis (Odds ratio (OR) for causing TBM 0.395, 95% confidence intervals (C.I.) 0.193-0.806, P = 0.009), suggesting these strains are less capable of extra-pulmonary dissemination than others in the study population. We also found that individuals with the C allele of TLR-2 T597C allele were more likely to have tuberculosis caused by the East-Asian/Beijing genotype (OR = 1.57 [95% C.I. 1.15-2.15]) than other individuals. The study provides evidence that M. tuberculosis genotype influences clinical disease phenotype and demonstrates, for the first time, a significant interaction between host and bacterial genotypes and the development of tuberculosis.
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spelling oxford-uuid:2cb15b84-165f-4a87-8f19-33e7dacf3b4c2022-03-26T12:38:45ZThe influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2cb15b84-165f-4a87-8f19-33e7dacf3b4cEnglishSymplectic Elements at Oxford2008Caws, MThwaites, GDunstan, SHawn, TLan, NThuong, NStepniewska, KHuyen, MBang, NLoc, TGagneux, Svan Soolingen, DKremer, Kvan der Sande, MSmall, PAnh, PChinh, NQuy, HDuyen, NTho, DHieu, NTorok, EHien, TDung, NNhu, NDuy, Pvan Vinh Chau, NFarrar, JThe factors that govern the development of tuberculosis disease are incompletely understood. We hypothesized that some strains of Mycobacterium tuberculosis (M. tuberculosis) are more capable of causing disseminated disease than others and may be associated with polymorphisms in host genes responsible for the innate immune response to infection. We compared the host and bacterial genotype in 187 Vietnamese adults with tuberculous meningitis (TBM) and 237 Vietnamese adults with uncomplicated pulmonary tuberculosis. The host genotype of tuberculosis cases was also compared with the genotype of 392 cord blood controls from the same population. Isolates of M. tuberculosis were genotyped by large sequence polymorphisms. The hosts were defined by polymorphisms in genes encoding Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and Toll-like receptor-2 (TLR-2). We found a significant protective association between the Euro-American lineage of M. tuberculosis and pulmonary rather than meningeal tuberculosis (Odds ratio (OR) for causing TBM 0.395, 95% confidence intervals (C.I.) 0.193-0.806, P = 0.009), suggesting these strains are less capable of extra-pulmonary dissemination than others in the study population. We also found that individuals with the C allele of TLR-2 T597C allele were more likely to have tuberculosis caused by the East-Asian/Beijing genotype (OR = 1.57 [95% C.I. 1.15-2.15]) than other individuals. The study provides evidence that M. tuberculosis genotype influences clinical disease phenotype and demonstrates, for the first time, a significant interaction between host and bacterial genotypes and the development of tuberculosis.
spellingShingle Caws, M
Thwaites, G
Dunstan, S
Hawn, T
Lan, N
Thuong, N
Stepniewska, K
Huyen, M
Bang, N
Loc, T
Gagneux, S
van Soolingen, D
Kremer, K
van der Sande, M
Small, P
Anh, P
Chinh, N
Quy, H
Duyen, N
Tho, D
Hieu, N
Torok, E
Hien, T
Dung, N
Nhu, N
Duy, P
van Vinh Chau, N
Farrar, J
The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis.
title The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis.
title_full The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis.
title_fullStr The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis.
title_full_unstemmed The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis.
title_short The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis.
title_sort influence of host and bacterial genotype on the development of disseminated disease with mycobacterium tuberculosis
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