Mycobacterium africanum elicits an attenuated T cell response to early secreted antigenic target, 6 kDa, in patients with tuberculosis and their household contacts
Mycobacterium africanum elicits an attenuated T cell response to early secreted antigenic target, 6 kDa, in patients with tuberculosis and their household contacts
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DOI：
10.1086/502977
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发表时间：
2006-05-01
影响因子：
6.4
通讯作者：
Adegbola, RA
中科院分区：
文献类型：
--
作者：
de Jong, BC;Hill, PC;Adegbola, RA
背景。非洲分枝杆菌是结核分枝杆菌复合体的一员，在西非以外很少发现，是那里一半结核病病例的病因。我们从结核病患者及其家庭接触者的研究中分离出的分枝杆菌进行基因分型，并通过感染基因型比较T细胞反应和结核菌素皮肤试验结果。与结核分枝杆菌感染患者相比，结核分枝杆菌感染患者（优势比[OR]， 0.41[95%可信区间{CI}， 0.19-0.89]; p = 0.024）和家庭接触者（OR, 0.56 [95% CI, 0.38-0.83]; p = 0.004）的T细胞对早期分泌抗原靶点6 kDa （ESAT-6）的反应减弱。在这些相同的组中，对培养滤液蛋白10 kDa （CFP-10）的反应无显著减弱（P = 0.22和P = 0.16），结核菌素皮肤试验结果也无显著减弱（P = 0.30和P = 0.46）。非洲支原体差异区1的测序结果表明，Rv3879c是非洲支原体的假基因；然而，这一发现并没有提供ESAT-6反应减弱的明显机制。据我们所知，这是菌株差异影响基于干扰素- γ的T细胞反应的第一个证据。我们的发现强调需要测试新的候选诊断针对不同菌株的分枝杆菌。将更多的结核分枝杆菌和非洲分枝杆菌的免疫学和基因组比较整合到进一步的研究中，可能为人类与分枝杆菌之间的相互作用提供基本的见解。
Background. Mycobacterium africanum, a member of the M. tuberculosis complex that is infrequently found outside of western Africa, is the cause of up to half of the tuberculosis cases there.Methods. We genotyped mycobacterial isolates obtained from a study of patients with tuberculosis and their household contacts and compared T cell responses and tuberculin skin test results by infecting genotype.Results. The T cell response to early secreted antigenic target, 6 kDa ( ESAT-6), was attenuated in patients with tuberculosis ( odds ratio [ OR], 0.41 [ 95% confidence interval {CI}, 0.19-0.89]; p = .024) and household contacts ( OR, 0.56 [ 95% CI, 0.38-0.83]; P = .004) infected with M. africanum, compared with the response in those infected with M. tuberculosis. In these same groups, responses to culture filtrate protein, 10 kDa ( CFP-10), were nonsignificantly attenuated (P = .22 and P = .16, respectively), as were tuberculin skin test results (p = .30 and P = .46, respectively). Sequencing of region of difference 1 of M. africanum revealed that Rv3879c is a pseudogene in M. africanum; however, this finding does not provide an obvious mechanism for the attenuated ESAT-6 response.Conclusions. This is the first evidence, to our knowledge, that strain differences affect interferon-gamma-based T cell responses. Our findings highlight the need to test new diagnostic candidates against different strains of mycobacteria. Integrating additional immunologic and genomic comparisons of M. tuberculosis and M. africanum into further studies may provide fundamental insights into the interactions between humans and mycobacteria.