Laboratory of Immunoregulation, Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.
J Infect Dis. 2010 Jan 1;201(1):62-70. doi: 10.1086/648615.
Most antigens from intracellular bacteria or vaccines induce both humoral and cell-mediated immune responses, but interactions between these responses are not fully understood. This study aims to resolve how specific antibodies participate in the activation of specific T cells in protecting hosts against Salmonella enterica serotype Typhimurium (S. typhimurium) infection.
Mice were administered anti-Salmonella immunoglobulin G (IgG) 1 day before Salmonella infection, and survival rate was observed. For in vitro assay, Salmonella bacteria were treated with anti-Salmonella IgG or control IgG before infection of the RAW264.7 or HEp2 cells. After infection, cell-associated bacteria number, induction of apoptosis, and production of nitric oxide were examined. In addition, antigen presentation assays using Salmonella-primed T cells were performed.
Treatment of S. typhimurium with anti-Salmonella IgG enhanced the macrophages' uptake of bacteria and induced high-frequency apoptotic cell death. In vitro antigen presentation assay revealed that the extracellular vesicles isolated from apoptotic cells caused by infection with anti-Salmonella IgG-treated S. typhimurium facilitated the responses of Salmonella-specific T cells.
Our findings suggest that humoral immunity cooperates with cell-mediated immunity upon induction of apoptosis in host cells to establish protective immunity against Salmonella infection, even if it does not directly eliminate intracellular microorganisms.
大多数来自细胞内细菌或疫苗的抗原既能诱导体液免疫反应,也能诱导细胞免疫反应,但这些反应之间的相互作用尚未完全阐明。本研究旨在解决特定抗体如何参与激活特定 T 细胞,以保护宿主免受鼠伤寒沙门氏菌(S. typhimurium)感染。
在沙门氏菌感染前一天给小鼠注射抗沙门氏菌 IgG,观察存活率。为了进行体外试验,用抗沙门氏菌 IgG 或对照 IgG 处理沙门氏菌,然后感染 RAW264.7 或 HEp2 细胞。感染后,检测细胞相关细菌数量、细胞凋亡诱导和一氧化氮产生情况。此外,还进行了使用经沙门氏菌致敏的 T 细胞的抗原呈递试验。
用抗沙门氏菌 IgG 处理鼠伤寒沙门氏菌可增强巨噬细胞对细菌的摄取,并诱导高频细胞凋亡。体外抗原呈递试验显示,用抗沙门氏菌 IgG 处理的 S. typhimurium 感染导致的细胞凋亡所分离的细胞外囊泡促进了沙门氏菌特异性 T 细胞的反应。
我们的研究结果表明,即使不能直接消除细胞内微生物,体液免疫也能与细胞免疫协同作用,在宿主细胞诱导凋亡的情况下建立对沙门氏菌感染的保护性免疫。