Smith D, Hänsch H, Bancroft G, Ehlers S
Department of Clinical Science, London School of Hygiene and Tropical Medicine, UK.
Immunology. 1997 Dec;92(4):413-21. doi: 10.1046/j.1365-2567.1997.00384.x.
We used Mycobacterium avium infection in severe combined immunodeficiency (SCID) mice to examine T-cell-independent mechanisms of inflammatory cell recruitment. SCID mice infected with a virulent strain of M. avium (TMC724) were able to recruit macrophages to sites of mycobacterial replication and formed organized and coherent granulomas in the absence of functional T cells. Phagocyte recruitment was almost totally ablated by neutralization of either tumour necrosis factor-alpha (TNF-alpha) or interferon-gamma (IFN-gamma) in vivo demonstrating that granuloma formation was dependent on the presence of these cytokines. This was concomitant with a reduction in the in situ cytokine mRNA levels otherwise induced in infected mice, for chemokines, pro-inflammatory and regulatory cytokines, including TNF-alpha, IFN-gamma, macrophage inflammatory protein-1 alpha, interleukin-1 beta (IL-1 beta) and IL-10. Furthermore, in vivo treatment of infected mice with anti-asialo GM-1 antisera, which depletes natural killer (NK) cells, prevented recruitment of inflammatory cells. In vitro studies confirmed that M. avium was able to elicit IFN-gamma from SCID spleen in a dose-dependent manner. These data show for the first time that secretion of IFN-gamma from NK cells can mediate a T-cell-independent pathway of granuloma formation and cellular infiltration in response to mycobacteria.
我们利用严重联合免疫缺陷（SCID）小鼠的鸟分枝杆菌感染来研究炎症细胞募集的非T细胞依赖机制。感染强毒株鸟分枝杆菌（TMC724）的SCID小鼠能够将巨噬细胞募集到分枝杆菌复制部位，并且在缺乏功能性T细胞的情况下形成有组织且连贯的肉芽肿。在体内通过中和肿瘤坏死因子-α（TNF-α）或干扰素-γ（IFN-γ），吞噬细胞的募集几乎完全被消除，这表明肉芽肿的形成依赖于这些细胞因子的存在。这与感染小鼠中原本诱导产生的趋化因子、促炎和调节细胞因子（包括TNF-α、IFN-γ、巨噬细胞炎性蛋白-1α、白细胞介素-1β（IL-1β）和IL-10）的原位细胞因子mRNA水平降低相伴发生。此外，用抗唾液酸GM-1抗血清对感染小鼠进行体内治疗，这种抗血清会消耗自然杀伤（NK）细胞，从而阻止炎症细胞的募集。体外研究证实，鸟分枝杆菌能够以剂量依赖的方式从SCID小鼠脾脏中诱导产生IFN-γ。这些数据首次表明，NK细胞分泌的IFN-γ可以介导对分枝杆菌产生反应时肉芽肿形成和细胞浸润的非T细胞依赖途径。
