Hirsch C S, Yoneda T, Averill L, Ellner J J, Toossi Z
Department of Medicine, Case Western Reserve University, University Hospitals of Cleveland.
J Infect Dis. 1994 Nov;170(5):1229-37. doi: 10.1093/infdis/170.5.1229.
The production of transforming growth factor-beta (TGF beta 1) by human monocytes (MN) infected with Mycobacterium tuberculosis and its effects on the intracellular fate of the organism were studied. M. tuberculosis infection of MN induced both expression of mRNA and secretion of tumor necrosis factor-alpha (TNF alpha) and TGF beta 1 protein. Neutralizing antibody to TGF beta 1 reduced the intracellular growth of M. tuberculosis. The growth-enhancing effects of TGF beta 1 could not be explained by increased initial bacterial load. Preculture with TGF beta 1 decreased uptake of M. tuberculosis. Exposure of MN to increasing concentrations of TGF beta 1 before or after infection with M. tuberculosis accelerated intracellular bacterial replication. Both TNF alpha and interferon-gamma (IFN-gamma) limited mycobacterial replication. TGF beta 1 (10 ng/mL) abrogated the bacteriostatic effects of TNF alpha and IFN-gamma. Within the infected focus, TGF beta 1 produced by mononuclear phagocytes may play an important role in the pathogenesis of tuberculosis, in part by modulating the response to potentially protective cytokines such as TNF alpha and IFN-gamma.
研究了感染结核分枝杆菌的人单核细胞（MN）产生转化生长因子-β（TGFβ1）的情况及其对该病原体细胞内命运的影响。结核分枝杆菌感染MN可诱导mRNA表达以及肿瘤坏死因子-α（TNFα）和TGFβ1蛋白的分泌。抗TGFβ1中和抗体可降低结核分枝杆菌的细胞内生长。TGFβ1的生长促进作用不能用初始细菌载量增加来解释。用TGFβ1预培养可减少结核分枝杆菌的摄取。在感染结核分枝杆菌之前或之后，将MN暴露于浓度不断增加的TGFβ1中会加速细胞内细菌复制。TNFα和干扰素-γ（IFN-γ）均限制分枝杆菌复制。TGFβ1（10 ng/mL）可消除TNFα和IFN-γ的抑菌作用。在感染灶内，单核吞噬细胞产生的TGFβ1可能在结核病发病机制中起重要作用，部分原因是通过调节对潜在保护性细胞因子如TNFα和IFN-γ的反应。
