Thuong N T T, Hawn T R, Thwaites G E, Chau T T H, Lan N T N, Quy H T, Hieu N T, Aderem A, Hien T T, Farrar J J, Dunstan S J
Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Genes Immun. 2007 Jul;8(5):422-8. doi: 10.1038/sj.gene.6364405. Epub 2007 Jun 7.
Tuberculous meningitis (TBM) results from the haematogenous dissemination of Mycobacterium tuberculosis from the lung to the brain. Dissemination is believed to occur early during infection, before the development of adaptive immunity. Toll-like receptor 2 (TLR2) mediates recognition of M. tuberculosis and initiates the innate immune response to infection. We hypothesized that polymorphisms in the TLR2 gene influence bacterial dissemination and the development of TBM. A case-control study was designed to test the hypothesis. Cases of bacteriologically confirmed pulmonary tuberculosis (TB) (n=183) and TBM (n=175), and cord blood controls (n=389) were enrolled in Vietnam. TLR2 genotype 597CC was associated with susceptibility to TB (odds ratio (OR)=2.22, 95% confidence interval (CI): 1.23-3.99). The association was found with meningeal rather than pulmonary TB (TBM vs control, OR=3.26, 95% CI: 1.72-6.18), and was strongest when miliary TB was found on chest radiography (controls vs TBM with miliary TB, OR=5.28, 95% CI: 2.20-12.65). Furthermore, the association increased with the severity of neurologic symptoms (grade I TBM, OR=1.93, 95% CI: 0.54-6.92; grade II, OR=3.32, 95% CI: 0.84-13.2; and grade III, OR=5.70, 95% CI: 1.81-18.0). These results demonstrate a strong association of TLR2 SNP T597C with the development of TBM and miliary TB and indicate that TLR2 influences the dissemination of M. tuberculosis.
结核性脑膜炎（TBM）是由结核分枝杆菌从肺部经血行播散至脑部所致。据信，播散发生在感染早期，即适应性免疫形成之前。Toll样受体2（TLR2）介导对结核分枝杆菌的识别，并启动针对感染的固有免疫反应。我们推测TLR2基因多态性会影响细菌播散及TBM的发生。为此设计了一项病例对照研究来验证这一假设。越南纳入了细菌学确诊的肺结核（TB）病例（n = 183）、TBM病例（n = 175）以及脐血对照（n = 389）。TLR2基因型597CC与TB易感性相关（比值比（OR）= 2.22，95%置信区间（CI）：1.23 - 3.99）。该关联在结核性脑膜炎而非肺结核中发现（TBM与对照相比，OR = 3.26，95% CI：1.72 - 6.18），且在胸部X线片发现粟粒性TB时最为显著（对照与伴有粟粒性TB的TBM相比，OR = 5.28，95% CI：2.20 - 12.65）。此外，该关联随神经症状严重程度增加而增强（I级TBM，OR = 1.93，95% CI：0.54 - 6.92；II级，OR = 3.32，95% CI：0.84 - 13.2；III级，OR = 5.70，95% CI：1.81 - 18.0）。这些结果表明TLR2单核苷酸多态性T597C与TBM及粟粒性TB的发生密切相关，并提示TLR2影响结核分枝杆菌的播散。
