title: 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.
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Rajen
authors.initials: R
authors.lastname: Patel
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Subash
authors.initials: S
authors.lastname: Sad
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D027682:Cation Transport Proteins / Q000235:genetics; D002478:Cells, Cultured; D045142:Cross-Priming; D003600:Cytosol / Q000378:metabolism; D003713:Dendritic Cells / Q000502:physiology; D004198:Disease Susceptibility; D057131:Immune Evasion; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010588:Phagosomes / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012485:Salmonella typhi / Q000276:immunology*; D014435:Typhoid Fever / Q000276:immunology*; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D027682:Cation Transport Proteins; D012097:Repressor Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1; C533289:SNFT protein, mouse