RESUMO
Typhoid fever and nontyphoidal bacteremia caused by Salmonella remain critical human health problems. B cells are required for protective immunity to Salmonella, but the mechanism of protection remains unclear. In this study, we immunized wild-type, B cell-deficient, Ab-deficient, and class-switched Ab-deficient mice with attenuated Salmonella and examined protection against secondary infection. As expected, wild-type mice were protected and B cell-deficient mice succumbed to secondary infection. Interestingly, mice with B cells but lacking secreted Ab or class-switched Ab had little deficiency in resistance to Salmonella infection. The susceptibility of B cell-deficient mice correlated with marked reductions in CD4 T cell IFN-γ production after secondary infection. Taken together, these data suggest that the primary role of B cells in acquired immunity to Salmonella is via the development of protective T cell immunity.
Assuntos
Anticorpos Antibacterianos/biossíntese , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/microbiologia , Infecções por Salmonella/prevenção & controle , Salmonella typhimurium/imunologia , Animais , Subpopulações de Linfócitos B/metabolismo , Imunidade Celular , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Camundongos Transgênicos , Infecções por Salmonella/imunologia , Infecções por Salmonella/patologia , Salmonella typhimurium/patogenicidade , Células Th1/imunologia , Células Th1/microbiologia , Virulência/imunologiaRESUMO
Pathogen-specific CD4 T cells are activated within a few hours of oral Salmonella infection and are essential for protective immunity. However, CD4 T cells do not participate in bacterial clearance until several weeks after infection, suggesting that Salmonella can inhibit or evade CD4 T cells that are activated at early time points. Here, we describe the progressive culling of initially activated CD4 T cells in Salmonella-infected mice. Loss of activated CD4 T cells was independent of early instructional programming, T cell precursor frequency, and Ag availability. In contrast, apoptosis of Ag-specific CD4 T cells was actively induced by live bacteria in a process that required Salmonella pathogenicity island-2 and correlated with increased expression of PD-L1. These data demonstrate efficient culling of initially activated Ag-specific CD4 cells by a microbial pathogen and document a novel strategy for bacterial immune evasion.