Dynamics of immune effector mechanisms during infection with Mycobacterium aviumin C57BL/6 mice
Dynamics of immune effector mechanisms during infection with Mycobacterium aviumin C57BL/6 mice
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DOI：
10.1111/imm.12131
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发表时间：
2013-10-01
期刊：
影响因子：
6.4
通讯作者：
Flo, Trude H.
中科院分区：
文献类型：
--
作者：
Haug, Markus;Awuh, Jane A.;Flo, Trude H.
摘要由于非结核分枝杆菌如鸟分枝杆菌引起的结核性感染的发病率增加和治疗困难，正重新受到人们的关注。至于其他分枝杆菌感染，仍然知之甚少的合作，不同的免疫效应机制，需要赋予保护性免疫。在这里，我们的特点是先天性和适应性免疫效应机制的相互作用，有助于遏制在小鼠感染模型中使用有毒M。禽流感病毒株104在C57 BL/6小鼠中的表达。M.禽流感病毒引起小鼠慢性感染，如持续的器官细菌负荷所示。在肝脏中，细菌包含在肉芽肿样结构中，其可以通过在相邻肝细胞和浸润中性粒细胞中表达抗菌先天效应蛋白Lipocalin 2在形态学上定义，可能有助于遏制。循环抗分枝杆菌抗体稳步增加整个感染，主要是IgM同种型。在感染后约2周，在感染小鼠的肝脏、脾脏和血清中发现最高水平的干扰素-γ，并且与器官细菌生长的停止相一致。相反，与肝脏相比，脾脏中肿瘤坏死因子的表达令人惊讶地低。在感染器官和M.禽特异性T辅助17细胞，表明T辅助17细胞在该模型中的次要作用。在脾脏中观察到调节性T细胞数量的短暂和相对减少。本文对M. C57 BL/6小鼠中的禽结核分枝杆菌感染可能为未来的研究提供基础，旨在更好地了解导致非结核分枝杆菌感染的机制。
SummaryOpportunistic infections with non-tuberculous mycobacteria such as Mycobacterium avium are receiving renewed attention because of increased incidence and difficulties in treatment. As for other mycobacterial infections, a still poorly understood collaboration of different immune effector mechanisms is required to confer protective immunity. Here we have characterized the interplay of innate and adaptive immune effector mechanisms contributing to containment in a mouse infection model using virulent M. avium strain 104 in C57BL/6 mice. M. avium caused chronic infection in mice, as shown by sustained organ bacterial load. In the liver, bacteria were contained in granuloma-like structures that could be defined morphologically by expression of the antibacterial innate effector protein Lipocalin 2 in the adjoining hepatocytes and infiltrating neutrophils, possibly contributing to containment. Circulatory anti-mycobacterial antibodies steadily increased throughout infection and were primarily of the IgM isotype. Highest levels of interferon-gamma were found in infected liver, spleen and serum of mice approximately 2 weeks post infection and coincided with a halt in organ bacterial growth. In contrast, expression of tumour necrosis factor was surprisingly low in spleen compared with liver. We did not detect interleukin-17 in infected organs or M. avium-specific T helper 17 cells, suggesting a minor role for T helper 17 cells in this model. A transient and relative decrease in regulatory T cell numbers was seen in spleens. This detailed characterization of M. avium infection in C57BL/6 mice may provide a basis for future studies aimed at gaining better insight into mechanisms leading to containment of infections with non-tuberculous mycobacteria.