Intracellular Salmonella inhibit antigen presentation by dendritic cells.
Dendritic cells (DC) are important APCs linking innate and adaptive immunity. During analysis of the intracellular activities of Salmonella enterica in DC, we observed that viable bacteria suppress Ag-dependent T cell proliferation. This effect was dependent on the induction of inducible NO synthase by DC and on the function of virulence genes in Salmonella pathogenicity island 2 (SPI2). Intracellular activities of Salmonella did not affect the viability, Ag uptake, or maturation of DC, but resulted in reduced presentation of antigenic peptides by MHC class II molecules. Increased resistance to reinfection was observed after vaccination of mice with SPI2-deficient Salmonella compared with mice vaccinated with SPI2-proficient Salmonella, and this correlated with an increased amount of CD4(+) as well as CD8(+) T cells. Our study is the first example of interference of an intracellular bacterial pathogen with Ag presentation by DC. The subversion of DC functions is a novel strategy deployed by this pathogen to escape immune defense, colonize host organs, and persist in the infected host.
Cheminay
Cédric
C
Institut für Klinische Mikrobiologie, Immunologie und Hygiene, Friedrich-Alexander Universität Erlangen-Nurnberg, Erlangen, Germany.
Möhlenbrink
Annette
A
Hensel
Michael
M
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001426:Bacterial Proteins / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D007113:Immunity, Innate / Q000276:immunology; D007165:Immunosuppression Therapy; D007424:Intracellular Fluid / Q000276:immunology* / Q000382:microbiology*; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000502:physiology; D008643:Mesentery; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D012481:Salmonella Infections, Animal / Q000276:immunology; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D001426:Bacterial Proteins; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; C440638:SPI-2 protein, Salmonella; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse