Macrophage and T cell dynamics during the development and disintegration of mycobacterial Granulomas
Macrophage and T cell dynamics during the development and disintegration of mycobacterial Granulomas
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DOI：
10.1016/j.immuni.2007.12.010
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发表时间：
2008-02-01
期刊：
影响因子：
32.4
通讯作者：
Germain, Ronald N.
中科院分区：
文献类型：
--
作者：
Egen, Jackson G.;Rothfuchs, Antonio Gigliotti;Germain, Ronald N.
肉芽肿在宿主抵抗分枝杆菌病原体的保护中起着关键作用，它们的分解会导致疾病的加重。为了更好地了解这些结构的启动和维护，我们采用了高分辨率的多重静态成像和活体多光子显微镜的牛分枝杆菌BCG诱导的肝肉芽肿。我们发现枯否细胞直接捕获血源性细菌，随后通过招募未感染的肝脏巨噬细胞和血液来源的单核细胞，使新生肉芽肿的形成成为核。在成熟的肉芽肿中，这些髓样细胞群形成了相对固定的细胞基质，与高度动态的效应T细胞群相互作用。这些T细胞的有效募集高度依赖于TNF-α衍生的信号，其也通过对未感染的巨噬细胞群体的优先作用来维持肉芽肿结构。通过表征肉芽肿发展过程中先天性和适应性免疫细胞的迁移，这些研究为分枝杆菌遏制和逃逸所涉及的细胞事件提供了新的视角。
Granulomas play a key role in host protection againstmycobacterial pathogens, with their breakdown contributing to exacerbated disease. To better understand the initiation and maintenance of these structures, we employed both high-resolution multiplex static imaging and intravital multiphoton microscopy of Mycobacterium bovis BCG-induced liver granulomas. We found that Kupffer cells directly capture blood-borne bacteria and subsequently nucleate formation of a nascent granuloma by recruiting both uninfected liver-resident macrophages and blood-derived monocytes. Within the mature granuloma, these myeloid cell populations formed a relatively immobile cellular matrix that interacted with a highly dynamic effector T cell population. The efficient recruitment of these T cells was highly dependent on TNF-alpha-derived signals, which also maintained the granuloma structure through preferential effects on uninfected macrophage populations. By characterizing the migration of both innate and adaptive immune cells throughout the process of granuloma development, these studies provide a new perspective on the cellular events involved in mycobacterial containment and escape.