B cell subsets are activated and produce cytokines during early phases of Francisella tularensis LVS infection

Francisella tularensis, a facultative intracellular Gram-negative bacterium, causes the illness tularemia. The infection of mice with live vaccine strain is considered to be a model of human tularemia. E tularensis infects predominantly such phagocytic cells as macrophages or neutrophils, but it also infects non-phagocytic hepatocytes, epithelial cells, and murine and human B cell lines. Based on work with the murine tularemia model, we report here that F. tularensis LVS infects peritoneal CD19(+) cells - exclusively B-la cells early after intraperitoneal infection in vivo. The peritoneal and consequently spleen CD19+ cells are activated by the F. tularensis LVS infection to express the activation markers from MHC class II, CD25, CD54, CD69, and the co-stimulatory molecules CD80 and CD86. As early as 12 h post-infection, the peritoneal CD19(+) cells produce IFN-gamma, IL-1 beta, IL-4, IL-6, IL-12, IL-17, IL-23, and THE-alpha. The spleen CD19(+) cells respond to infection with some delay. Moreover, the E tularensis infected A20 B cell line activates CD3(+) spleen cells isolated from naive mice. Thus, the data presented here suggest that B cells have all the attributes to actively participate in the induction and regulation of the adaptive immune response during early stages of E tularensis infection. (C) 2014 Elsevier Ltd. All rights reserved.