Abstract
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.
Highlights
It is estimated that one third of the world’s population is infected with Mycobacterium tuberculosis (M. tuberculosis), the majority will never develop active disease
In this study we show that some strains of M. tuberculosis commonly found in Europe and America are less likely to cause tuberculous meningitis in Vietnamese adults than strains predominantly found in Asia
To investigate whether different strains of M. tuberculosis are associated with disseminated disease, we examined isolates from HIV-negative adult patients in Vietnam who either had meningeal disease (n = 187) or localized pulmonary TB (n = 237)
Summary
It is estimated that one third of the world’s population is infected with Mycobacterium tuberculosis (M. tuberculosis), the majority will never develop active disease. The factors that govern the development of tuberculosis disease are complex and incompletely understood. Various factors have been clearly associated with increased susceptibility to tuberculosis. Defining the contribution of host genetic polymorphisms to disease susceptibility has been more difficult. Studies have suggested polymorphisms in several genes are associated with the development of pulmonary tuberculosis. Others have shown the less common extrapulmonary manifestations of tuberculosis may have a different host genetic susceptibility profile and have implicated various polymorphism in components of the innate host response to infection [15] [16,17] [18,19].
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