Intragranulomatous necrosis in lungs of mice infected by aerosol with Mycobacterium tuberculosis is related to bacterial load rather than to any one cytokine or T cell type
Intragranulomatous necrosis in lungs of mice infected by aerosol with Mycobacterium tuberculosis is related to bacterial load rather than to any one cytokine or T cell type
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DOI：
10.1016/j.micinf.2005.08.014
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发表时间：
2006-03-01
影响因子：
5.8
通讯作者：
Cardona, Pere-Joan
中科院分区：
文献类型：
--
作者：
Gil, Olga;Guirado, Evelyn;Cardona, Pere-Joan
用结核分枝杆菌临床菌株（UTE 0335R）对C57BL/6小鼠进行低剂量气溶胶感染，在感染后第9周诱发肺肉芽肿内坏死（INPG）。用UTE 0335R感染不同基因敲除（KO）小鼠品系，在所有品系中均诱发了INPG，并呈现出两种组织病理学模式。第一种模式见于严重联合免疫缺陷（SCID）小鼠以及α/β T细胞受体、肿瘤坏死因子受体1（TNF R1）、白细胞介素 - 12（IL - 12）、干扰素 - γ（IFN - γ）或一氧化氮合酶（NOS）基因缺失的小鼠，表现为大量的INPG，肺部有高度的肉芽肿浸润，大面积均匀的嗜酸性坏死灶内充满抗酸杆菌，伴有明显的核破裂、粗的嗜碱性坏死，周围是由充满多形核中性粒细胞（PMNs）且部分保存的肺泡隔界定的斑块。第二种模式见于白细胞介素 - 1受体1（IL - 1R1）、白细胞介素 - 6（IL - 6）、白细胞介素 - 10（IL - 10）、CD4、CD8或γ/δ T细胞受体基因缺失的小鼠，表现为更离散的病变，主要为均匀的嗜酸性坏死，杆菌较少，周围是界限分明的以淋巴细胞为主的环。干扰素 - γ、一氧化氮合酶、肿瘤坏死因子和调节激活正常T细胞表达和分泌因子（RANTES）的局部表达在这些产生离散INPG的小鼠品系之间无显著差异。与对照品系相比，表现为大量INPG的小鼠品系呈现出更高、更低或相等的表达值。总之，INPG模式的严重程度与肺部菌落形成单位（CFU）计数相关，与细胞因子介质的基因缺失情况或感染诱导的水平无关。（c）2006爱思唯尔SAS。保留所有权利。
Low dose aerosol infection of C5713L/6 mice with a clinical strain of Mycobacterium tuberculosis (UTE 0335 R) induced intragranulomatous necrosis in pulmonary granulomas (INPG) at week 9 postinfection. Infection of different knockout (KO) mouse strains with UTE 0335 R induced INPG in all strains and established two histopathological patterns. The first pattern was seen in SCID mice and in mice with deleted alpha/beta T receptor, TNF R1, IL-12, IFN-gamma, or NOS genes, and showed a massive INPG with a high granulomatous infiltration of the lung, a large and homogeneous eosinophilic necrosis full of acid-fast bacilli, with marked karyorrhexis, coarse basophilic necrosis, and surrounded by patches delimited by partially conserved alveolar septum full of PMNs. The second pattern was seen in mice with deleted IL-1 R1, IL-6, IL-10, CD4, CD8 or gamma/delta T cell receptor genes, and showed more discrete lesions with predominant homogeneous eosinophilic necrosis with few bacilli and surrounded by a well-defined lymphocyte-based ring. Local expression of IFN-gamma, NOS, TNF and RANTES showed no significant differences between these mouse strains generating a discrete INPG. Mouse strains showing a massive INPG showed higher, lower or equal expression values compared to the control strain. In conclusion, the severity of the INPG pattern correlated with pulmonary CFU counts, irrespective of the genetic absence or the infection-induced levels of cytokine mediators. (c) 2006 Elsevier SAS. All rights reserved.