Binding of Salmonella-Specific Antibody Facilitates Specific T Cell Responses via Augmentation of Bacterial Uptake and Induction of Apoptosis in Macrophages

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.