Distinct responses of splenic dendritic cell subsets to infection with Listeria monocytogenes: maturation phenotype, level of infection, and T cell priming capacity ex vivo |
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Authors: | Mitchell L M Brzoza-Lewis K L Henry C J Grayson J M Westcott M M Hiltbold E M |
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Institution: | Departments of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA |
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Abstract: | To determine the relative contributions of DC subsets in the development of protective immunity to Listeria monocytogenes we examined the relationship between maturation, bacterial burden, and T cell priming capacity of four well characterized subsets of splenic DC following infection with Lm. CD8α+, CD4+, and CD8α−CD4− DC and the B220+ plasmacytoid DC (pDC) were compared for abundance and costimulatory molecule expression at 24, 48, and 72 h post i.v. infection. We further determined the bacterial burden associated with each DC subset and their relative capacities to prime CD8+ T cells at 24 hpi. The CD8α+ DC displayed the highest level of maturation, association with live bacteria, and T cell activation potential. Second, the CD4+ DC were also mature, yet were associated with fewer bacteria, and stimulated T cell proliferation, but not IFN-γ production. The CD8α−CD4− DC showed a modest maturation response and were associated with a high number of bacteria, but failed to induce T cell proliferation ex vivo. pDC displayed a strong maturation response, but were not associated with detectable bacteria and also failed to stimulate T cell activation. Finally, we measured the cytokine responses in these subsets and determined that IL-12 was produced predominantly by the CD8+ DC, correlating with the ability of this subset DC to induce IFN-γ production in T cells. We conclude that Listeria-specific CD8+ T cell activation in the spleen is most effectively achieved by infection-induced maturation of the CD8α+ DC subset. |
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Keywords: | Dendritic cells Listeria T cell activation Costimulation Innate immunity |
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