Different innate ability of I/St and A/Sn mice to combat virulent Mycobacterium tuberculosis:: Phenotypes expressed in lung and extrapulmonary macrophages
Different innate ability of I/St and A/Sn mice to combat virulent Mycobacterium tuberculosis:: Phenotypes expressed in lung and extrapulmonary macrophages
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DOI：
10.1128/iai.71.2.697-707.2003
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发表时间：
2003-02-01
影响因子：
3.1
通讯作者：
Apt, AS
中科院分区：
文献类型：
--
作者：
Majorov, KB;Lyadova, IV;Apt, AS
I/St和A/Sn近交系小鼠分别表现出由结核分枝杆菌引起的严重和中度疾病。先前，我们发现与A/Sn小鼠相比，I/St小鼠对分枝杆菌抗原的反应转向th2样反应性和更高的增殖活性和T细胞周转率。然而，这些小鼠结核病严重程度的不同表达的生理基础在很大程度上仍然未知。在此，我们扩展了之前的观察结果，证明I/St间质肺巨噬细胞在体外感染结核分枝杆菌H37Rv后抑制分枝杆菌生长和存活的能力存在缺陷。这种表型的一个独特特征是它在新鲜分离的肺巨噬细胞中独家表达。从腹膜腔中获得的离体巨噬细胞和从各种器官（包括肺本身）提取的祖细胞体外培养的巨噬细胞都不会出现这种缺陷。此外，我们发现，与腹膜巨噬细胞形成鲜明对比的是，肺巨噬细胞的分枝杆菌杀灭能力在外源性γ干扰素存在下不会升高。我们的数据表明，在特定解剖微环境中的体内分化决定了巨噬细胞-分枝杆菌相互作用的模式。因此，当基于在特定体外系统中获得的结果得出的结论被推广到结核分枝杆菌感染期间所有吞噬细胞的功能时，应谨慎行事。
Mice of the I/St and A/Sn inbred strains display a severe and moderate course, respectively, of disease caused by Mycobacterium tuberculosis. Earlier, we showed that the response to mycobacterial antigens in I/St mice compared to that in A/Sn mice is shifted toward Th2-like reactivity and a higher proliferative activity and turnover of T cells. However, the physiologic basis for different expressions of tuberculosis severity in these mice remains largely unknown. Here, we extend our previous observations with evidence that I/St interstitial lung macrophages are defective in the ability to inhibit mycobacterial growth and to survive following in vitro infection with M. tuberculosis H37Rv. A unique feature of this phenotype is its exclusive expression in freshly isolated lung macrophages. The defect is not displayed in ex vivo macrophages obtained from the peritoneal cavity nor in macrophages developed in vitro from progenitors extracted from various organs, including the lung itself. In addition, we show that, in sharp contrast to peritoneal macrophages, the mycobactericidal capacity of lung macrophages is not elevated in the presence of exogenous gamma interferon. Our data suggest that the in vivo differentiation in a particular anatomical microenvironment determines the pattern of macrophage-mycobacterium interaction. Thus, caution should be exercised when conclusions based upon the results obtained in a particular in vitro system are generalized to the functions of all phagocytes during M. tuberculosis infection.