Host genetics in granuloma formation: human-like lung pathology in mice with reciprocal genetic susceptibility to M. tuberculosis and M. avium.
Host genetics in granuloma formation: human-like lung pathology in mice with reciprocal genetic susceptibility to M. tuberculosis and M. avium.
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DOI：
10.1371/journal.pone.0010515
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发表时间：
2010-05-06
期刊：
影响因子：
3.7
通讯作者：
Apt A
中科院分区：
文献类型：
--
作者：
Kondratieva E;Logunova N;Majorov K;Averbakh M;Apt A
肺肉芽肿的发展是由毒性分枝杆菌引起的感染的标志，反映了限制感染传播的保护性宿主反应和炎症病理。宿主遗传学在肉芽肿形成中的作用还不明确。早先我们已经证明，I/St品系的小鼠对结核分枝杆菌极其敏感，但对M.禽流感病毒感染，而B6小鼠表现出相反的易感性模式。在这里，通过直接比较：（i）对两种感染的易感性特征;（ii）通过免疫染色评估肺肉芽肿的结构;（iii）编码肺组织中中性粒细胞流入调节因子的基因的表达，我们证明宿主的遗传易感性在很大程度上决定了肺病理学的模式。M.肺内出现坏死性肉芽肿，周围有缺氧区，同时有大量中性粒细胞流入。B6小鼠和M.肺结核感染的I/St小鼠，但不是在相应的遗传耐药对应的肺。肺组织对两种强毒分枝杆菌的镜像反应表明，宿主对给定分枝杆菌种的遗传易感性水平在很大程度上决定了病理学特征，并直接表明宿主遗传学在发病机制中的重要性。
Development of lung granulomata is a hallmark of infections caused by virulent mycobacteria, reflecting both protective host response that restricts infection spreading and inflammatory pathology. The role of host genetics in granuloma formation is not well defined. Earlier we have shown that mice of the I/St strain are extremely susceptible to Mycobacterium tuberculosis but resistant to M. avium infection, whereas B6 mice show a reversed pattern of susceptibility. Here, by directly comparing: (i) characteristics of susceptibility to two infections in vivo; (ii) architecture of lung granulomata assessed by immune staining; and (iii) expression of genes encoding regulatory factors of neutrophil influx in the lung tissue, we demonstrate that genetic susceptibility of the host largely determines the pattern of lung pathology. Necrotizing granuloma surrounded by hypoxic zones, as well as a massive neutrophil influx, develop in the lungs of M. avium-infected B6 mice and in the lungs of M. tuberculosis-infected I/St mice, but not in the lungs of corresponding genetically resistant counterparts. The mirror-type lung tissue responses to two virulent mycobacteria indicate that the level of genetic susceptibility of the host to a given mycobacterial species largely determines characteristics of pathology, and directly demonstrate the importance of host genetics in pathogenesis.
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DOI：
10.1054/tuld.1999.0225
发表时间：
2000-01-01
期刊：
TUBERCLE AND LUNG DISEASE
影响因子：
--
作者：
Nikonenko, BV;Averbakh, MM;Apt, AS
通讯作者：
Apt, AS
影响因子：
3.1
作者：
Fulton, SA;Reba, SM;Boom, WH
通讯作者：
Boom, WH
影响因子：
5.8
作者：
Flynn, JoAnne L.
通讯作者：
Flynn, JoAnne L.
影响因子：
4.4
作者：
Ehlers, S;Kutsch, S;Pfeffer, K
通讯作者：
Pfeffer, K
影响因子：
3.1
作者：
Majorov, KB;Lyadova, IV;Apt, AS
通讯作者：
Apt, AS