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The Influence of Host and Bacterial Genotype on the Development of Disseminated Disease with Mycobacterium tuberculosis

2008; Public Library of Science; Volume: 4; Issue: 3 Linguagem: Inglês

10.1371/journal.ppat.1000034

1553-7374

Maxine Caws, Guy Thwaites, Sarah J. Dunstan, Thomas R. Hawn, Nguyễn Thị Ngọc Lan, Nguyễn Thụy Thương Thương, Kasia Stepniewska, Mai Nguyet Thu Huyen, Nguyen Duc Bang, Tran Huu Loc, Sébastien Gagneux, Dick van Soolingen, Kristin Kremer, Marianne A. B. van der Sande, Peter M. Small, Phan Thi Hoang Anh, Nguyen Tran Chinh, Hoang Thi Quy, Nguyen Thi Duyen, Dau Quang Tho, Nguyen Trong Hieu, M. Estée Török, Tran Tinh Hien, Nguyen Huy Dung, Nguyen Thi Quynh Nhu, Minh‐Duy Phan, Nguyễn Văn Vĩnh Châu, Jeremy Farrar,

Pneumonia and Respiratory Infections

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.