Roles of type II alveolar epithelial cells in T cell-dependent immune response in Mycobacterium tuberculosis infection

II型肺泡上皮细胞在结核分枝杆菌感染中T细胞依赖性免疫应答中的作用

• 批准号: 13670601
• 负责人: SATO Katsumasa
• 金额: $ 2.3万
• 依托单位: SHIMANE MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670601/
• 关键词: M.tuberculosis; M.avium complex; type II alveolar pneumocytes; lymphocytes; macrophages; A-549 cells; PBMC; cytokines; M. avium complex; リンパ酸

Our previous study revealed that both Mycobacterium tuberculosis (MTB) and M.avium complex (MAC) organisms invade type II alveolar epithelial cells in the lungs when mice are subjected to mycobacterial challenge via the intracheal route. In addition, MTB- or MAC-infected A-549 human type II alveolar epithelial cells (A-549 cells) release humoral factors (TNF-α and GM-CSF), thereby increasing antimycobacterial activity of macrophages(Mφs). In this study, the following findings have been obtained. (1) Anti-TNF-α and anti-GM-CSF antibodies attenuated A-549 cell-dependent inhibition of the intramacrophage growth of MTB and MAC, indicating crucial roles of these cytokines in A-549 cell-mediated potentiation of Mφ antimycobacterial activity. (2) When human peripheral blood mononuclear cells (PBMC) were added onto MTB-infected A-549 cells and Con A- or PPD-induced T cell mitogenesis was examined, T cell mitogenosis in the presence of A-549 cells was inhibited more profoundly than cases without A-549 cells. Such an inhibitory effect was also observed for A-549 cells without MTB infection. When a dual chamber system was used to prevent the cell contact between PBMC and A-549 cells, similar results were also obtained. Therefore, it is thought that the observed inhibition of PBMC mitogenesis due to A-549 cells is dependent upon some unknown humoral T cell-inhibitory factors released from A-549 cells.

我们以前的研究表明，结核分枝杆菌（MTB）和鸟分枝杆菌复合体（MAC）生物体侵入肺中的II型肺泡上皮细胞时，小鼠通过气管内途径进行分枝杆菌的挑战。此外，MTB或MAC感染的A-549人II型肺泡上皮细胞（A-549细胞）释放体液因子（TNF-α和GM-CSF），从而增加巨噬细胞（Mφ）的抗分枝杆菌活性。在这项研究中，获得了以下发现。(1)抗TNF-α和抗GM-CSF抗体减弱了A-549细胞对MTB和MAC巨噬细胞内生长的细胞依赖性抑制，表明这些细胞因子在A-549细胞介导的Mφ抗结核杆菌活性增强中发挥着关键作用。(2)当人外周血单个核细胞（PBMC）被添加到MTB感染的A-549细胞和Con A-或PPD诱导的T细胞有丝分裂被检查，T细胞有丝分裂在A-549细胞的存在下被抑制比没有A-549细胞的情况下更深刻。在没有MTB感染的A-549细胞中也观察到这种抑制作用。当使用双室系统来防止PBMC和A-549细胞之间的细胞接触时，也获得了类似的结果。因此，认为观察到的A-549细胞对PBMC有丝分裂的抑制依赖于A-549细胞释放的一些未知的体液T细胞抑制因子。

项目成果

冨岡治明: "細菌学(竹田美文,林 英生 編)、分担執筆"朝倉書店. 563-572 (2002)

富冈晴明：《细菌学》（武田吉文和林秀夫编辑），合著者《朝仓书店》563-572 (2002)。

冨岡治明: "細菌学(竹田美文, 林 英生 編)、分担執筆"朝倉書店. 563-572 (2002)

富冈晴明：《细菌学》（武田吉文和林秀夫编辑），合著者《朝仓书店》563-572 (2002)。

Tomioka H, Sato K, Shimizu T, Sano C: "Anti-Mycobacterium tuberculosis activities of new fluoroquinolones in combination with other antituberculous drugs"J Infection. 44. 160-165 (2002)

Tomioka H、Sato K、Shimizu T、Sano C：“新型氟喹诺酮类药物与其他抗结核药物联合使用的抗结核分枝杆菌活性”J 感染。

Tomioka H, Shimizu T, Sato K, et al.: "Expression profiles of low molecular mass heat shock proteins by Mycobacterium avium and Mycodacterium intracellulare"FEMS Microbiology Letters. 200. 131-136 (2001)

Tomioka H、Shimizu T、Sato K 等人：“鸟分枝杆菌和胞内分枝杆菌的低分子量热休克蛋白的表达谱”FEMS 微生物学快报。

Sato K, Tomioka T, Shimizu K, et al.: "Type II alveolar cells play roles in macrophage-mediated host innate resistance to pulmonary mycobacterial infections by producing proinflammatory cytokines"The Journal of Infectious Diseases. (in press). (2002)

Sato K、Tomioka T、Shimizu K 等人：“II 型肺泡细胞通过产生促炎细胞因子，在巨噬细胞介导的宿主对肺部分枝杆菌感染的先天抵抗中发挥作用”《传染病杂志》。