Manca C, Tsenova L, Barry C E, Bergtold A, Freeman S, Haslett P A, Musser J M, Freedman V H, Kaplan G
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York 10021, USA.
J Immunol. 1999 Jun 1;162(11):6740-6.
Mycobacterium tuberculosis CDC1551, a clinical isolate reported to be hypervirulent and to grow faster than other isolates, was compared with two other clinical isolates (HN60 and HN878) and two laboratory strains (H37Rv and Erdman). The initial (1-14 days) growth of CDC1551, HN60, HN878, and H37Rv was similar in the lungs of aerosol-infected mice, but growth of Erdman was slower. Thereafter, the growth rate of CDC1551 decreased relative to the other strains which continued to grow at comparable rates up to day 21. In the lungs of CDC1551-infected mice, small well-organized granulomas with high levels of TNF-alpha, IL-6, IL-10, IL-12, and IFN-gamma mRNA were apparent sooner than in lungs of mice infected with the other strains. CDC1551-infected mice survived significantly longer. These findings were confirmed in vitro. The growth rates of H37Rv and CDC1551 in human monocytes were the same, but higher levels of TNF-alpha, IL-10, IL-6, and IL-12 were induced in monocytes after infection with CDC1551 or by exposure of monocytes to lipid fractions from CDC1551. CD14 expression on the surface of the monocytes was up-regulated to a greater extent by exposure to the lipids of CDC1551. Thus, CDC1551 is not more virulent than other M. tuberculosis isolates in terms of growth in vivo and in vitro, but it induces a more rapid and robust host response.
结核分枝杆菌CDC1551是一株临床分离株,据报道具有高毒力且生长速度比其他分离株快。将其与另外两株临床分离株(HN60和HN878)以及两株实验室菌株(H37Rv和Erdman)进行了比较。在气溶胶感染小鼠的肺部,CDC1551、HN60、HN878和H37Rv的初期(1 - 14天)生长情况相似,但Erdman的生长较慢。此后,相对于其他菌株,CDC1551的生长速率下降,而其他菌株在第21天前继续以相当的速率生长。在感染CDC1551的小鼠肺部,与感染其他菌株的小鼠肺部相比,更早出现了组织良好的小肉芽肿,其中TNF-α、IL-6、IL-10、IL-12和IFN-γ mRNA水平较高。感染CDC1551的小鼠存活时间明显更长。这些发现在体外得到了证实。H37Rv和CDC1551在人单核细胞中的生长速率相同,但感染CDC1551后或使单核细胞暴露于CDC1551的脂质组分后,单核细胞中诱导产生的TNF-α、IL-10、IL-6和IL-12水平更高。暴露于CDC1551的脂质后,单核细胞表面CD14的表达上调程度更大。因此,就体内和体外生长而言,CDC1551的毒力并不比其他结核分枝杆菌分离株更强,但它能诱导更快速、更强有力的宿主反应。