Transcription factor Batf3 is important for development of CD8+ T-cell response against a phagosomal bacterium regardless of the location of antigen.

Abstract

Salmonella enterica serovar Typhimurium (ST) is a virulent intracellular bacterium that conceals itself in the phagosomes of infected cells. Although CD8(+) T cells promote protection against various intracellular pathogens, the role of CD8(+) T cells against virulent ST has been unclear due to early fatality of susceptible (B6) mice. Herein, we generated MHC I-deficient mice on the resistant (129SvJ) and susceptible (Nramp1 transgenic B6) background to evaluate the role of CD8(+) T cells against virulent ST. Our results indicate that CD8(+) T cells have a critical protective role in host survival during infection with virulent ST. As antigen presentation and CD8(+) T-cell activation against phagosomal antigens are considered to operate through the cross-presentation pathway, we have evaluated CD8(+) T-cell response against ST in Batf3-deficient mice that lack CD8α dendritic cells (DCs). Using a recombinant of ST that expresses antigen (ST-OVA) mainly in the phagosomes of infected cells, we show that CD8(+) T-cell response is compromised throughout the duration of infection in Batf3-deficient mice. In contrast, when ST delivers antigen to the cytosol of infected cells (ST-OVA-C), CD8(+) T-cell response against the cytosolic antigen was compromised only in the short term in the absence of CD8α DCs, with wild-type and Batf3-deficient mice generating similar CD8(+) T-cell response in the long term. Thus, Batf3 has an important role in CD8(+) T-cell priming regardless of antigenic location; however, its role is redundant at later time intervals against cytosolic antigen.