Sanquin Research and Landsteiner Laboratory, Department of Immunopathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
PLoS One. 2010 Sep 27;5(9):e13016. doi: 10.1371/journal.pone.0013016.
The eradication of facultative intracellular bacterial pathogens, like Salmonella typhi, requires the concerted action of both the humoral immune response and the cytotoxic CD8(+) T cell response. Dendritic cells (DCs) are considered to orchestrate the cytotoxic CD8(+) T cell response via cross-presentation of bacterial antigens onto MHC class I molecules. Cross-presentation of Salmonella by DCs however, is accompanied by the induction of apoptosis in the DCs. Besides antibody production, B cells are required to clear Salmonella infection for other unknown reasons.
METHODOLOGY/PRINCIPAL FINDINGS: Here we show that Salmonella-specific B cells that phagocytose Salmonella upon BCR-ligation reactivate human memory CD8(+) T cells via cross-presentation yielding a Salmonella-specific cytotoxic T cell response. The reactivation of CD8(+) T cells is dependent on CD4(+) T cell help. Unlike the DCs, B cell-mediated cross-presentation of Salmonella does not coincide with apoptosis.
CONCLUSIONS/SIGNIFICANCE: B cells form a new player in the activation of the cytotoxic effector arm of the immune response and the generation of effective adaptive immunity in Salmonella infection.
兼性细胞内细菌病原体(如伤寒沙门氏菌)的消除需要体液免疫反应和细胞毒性 CD8(+) T 细胞反应的协同作用。树突状细胞 (DC) 被认为通过将细菌抗原呈递到 MHC 类 I 分子上来协调细胞毒性 CD8(+) T 细胞反应。然而,DC 对沙门氏菌的交叉呈递伴随着 DC 凋亡的诱导。除了抗体产生外,B 细胞还需要清除沙门氏菌感染,原因尚不清楚。
方法/主要发现:在这里,我们表明,在 BCR 交联时吞噬沙门氏菌的沙门氏菌特异性 B 细胞通过交叉呈递重新激活人类记忆 CD8(+) T 细胞,产生沙门氏菌特异性细胞毒性 T 细胞反应。CD8(+) T 细胞的再激活依赖于 CD4(+) T 细胞的辅助。与 DC 不同,B 细胞介导的沙门氏菌交叉呈递与凋亡不同时发生。
结论/意义:B 细胞在沙门氏菌感染中激活免疫反应的细胞毒性效应器臂和产生有效适应性免疫方面形成了一个新的参与者。