Differential involvement of dendritic cell subsets during acute Salmonellainfection

Within murine CD11c(+) dendritic cells (DC), CD8 alpha (+), CD8 alpha (-)CD 4(+), and CD8 alpha (-)CD4(-) subsets are defined. This study, characterize d the localization, number, and function of these subsets during acute Salm onella typhimuritun infection. Immunohistochemical and flow cytometric anal yses of spleens from mice orally infected with virulent S. typhimurium reve aled that in situ redistribution and alteration in the absolute number and function of DC occurred in a subset-specific manner during infection. CD8 a lpha (-)CD4(+) DC present at B cell follicle borders in the spleen of naive mice were absent 5 days post-Salmonella infection, despite no overall chan ge in the absolute number of CD8 alpha (-)CD4(+) splenic DC. CD8 alpha (+) and CD8 alpha (-)CD4(-) DC were prominently associated with the red pulp, a nd the frequency of these cells increased strikingly 5 days post-Salmonella infection. Significant quantitative increases in both CD8 alpha (+) and CD 8 alpha (-)CD4(-) subsets were associated with the in situ redistribution. Examination of Salmonella-infected TAP1(-1-)/beta (2)-microglobulin(-l-) mi ce, which lack CD8 alpha (+) T cells, confirmed the differential subset-spe cific modulations in the DC populations both in situ and quantitatively. Ex vivo intracellular cytokine analysis showed significantly increased freque ncies of CD8 alpha (+) DC producing TNF-alpha at days 2 and 5 postinfection . In contrast, CD4(+) DC producing TNF-alpha were transiently, increased fo llowed by a significant reduction. No significant increase in IL-12p40 or I L-10 production by splenic DC was detected during the first 5 days post-S. typhimurium infection. Together these data reveal differential modulation o f splenic DC subsets with regard to organization, number, and cytokine prod uction during the course of acute Salmonella infection.