Byrd T F
Department of Medicine, Albuquerque Veterans Affairs Medical Center, Albuquerque, New Mexico, 87108, USA.
Cell Immunol. 1998 Sep 15;188(2):89-96. doi: 10.1006/cimm.1998.1352.
One of the hallmarks of an effective immune response against Mycobacterium tuberculosis is the formation of granulomas containing multinucleated giant cells. IFN-gamma and interleukin-3 (IL-3) promote Langhans-type multinucleated giant cell formation and have been identified in T cell clones reacting to M. tuberculosis antigens. The ability of human monocytes treated with IFN-gamma and IL-3 to limit the spread of M. tuberculosis in an in vitro infection assay was examined. Monocytes were incubated with control medium, IFN-gamma, TNF-alpha, and calcitriol, a combination permissive to M. tuberculosis growth, or IFN-gamma and IL-3 and infected with a low inoculum of M. tuberculosis (Erdman). IFN-gamma/IL-3 treatment reduced M. tuberculosis CFU relative to both untreated and IFN-gamma/TNF-alpha/calcitriol-treated monocytes. Specifically, CFU were reduced by 79% at 14 days in the IFN-gamma/IL-3 treatment group relative to the IFN-gamma/TNF-alpha/calcitriol treatment group, an effect that was not due to toxic monocyte metabolites. M. tuberculosis growth restriction by IFN-gamma/IL-3-treated monocyte monolayers was associated with the development of Langhans-type multinucleated giant cells. At the light microscope level, dense growth of M. tuberculosis surrounded by a ring of nuclei localized to the center of individual cells. The intracellular location of M. tuberculosis was confirmed by electron microscopy. In contrast, monocyte monolayers treated with IFN-gamma/TNF-alpha/calcitriol consisted of a syncitium of cells containing monocyte aggregates. Nonlocalized linear arrays of M. tuberculosis were observed to be growing throughout such aggregates. These results suggest that physical sequestration of M. tuberculosis by Langhans-type multinucleated giant cells may limit cell to cell spread of this pathogen, thereby restricting growth.
针对结核分枝杆菌的有效免疫反应的一个标志是形成含有多核巨细胞的肉芽肿。干扰素-γ和白细胞介素-3（IL-3）促进朗汉斯型多核巨细胞的形成，并且已在对结核分枝杆菌抗原产生反应的T细胞克隆中得到确认。研究了用干扰素-γ和IL-3处理的人单核细胞在体外感染试验中限制结核分枝杆菌传播的能力。将单核细胞与对照培养基、干扰素-γ、肿瘤坏死因子-α和骨化三醇（一种允许结核分枝杆菌生长的组合）或干扰素-γ和IL-3一起孵育，并用低接种量的结核分枝杆菌（埃尔德曼菌株）进行感染。相对于未处理的单核细胞和用干扰素-γ/肿瘤坏死因子-α/骨化三醇处理的单核细胞，干扰素-γ/IL-3处理降低了结核分枝杆菌的菌落形成单位（CFU）。具体而言，相对于干扰素-γ/肿瘤坏死因子-α/骨化三醇处理组，干扰素-γ/IL-3处理组在14天时CFU减少了79%，这种效应并非由于单核细胞的毒性代谢产物所致。干扰素-γ/IL-3处理的单核细胞单层对结核分枝杆菌生长的限制与朗汉斯型多核巨细胞的形成有关。在光学显微镜水平上，结核分枝杆菌密集生长，被一圈细胞核包围，位于单个细胞的中心。结核分枝杆菌的细胞内定位通过电子显微镜得到证实。相比之下，用干扰素-γ/肿瘤坏死因子-α/骨化三醇处理的单核细胞单层由含有单核细胞聚集体的细胞融合体组成。观察到结核分枝杆菌的非定位线性阵列在整个此类聚集体中生长。这些结果表明，朗汉斯型多核巨细胞对结核分枝杆菌的物理隔离可能限制了该病原体在细胞间的传播，从而限制其生长。
