Differential Involvement of Dendritic Cell Subsets During Acute Salmonella Infection

Abstract

Within murine CD11c+ dendritic cells (DC), CD8α+, CD8α−CD4+, and CD8α−CD4− subsets are defined. This study characterized the localization, number, and function of these subsets during acute Salmonella typhimurium infection. Immunohistochemical and flow cytometric analyses of spleens from mice orally infected with virulent S. typhimurium revealed that in situ redistribution and alteration in the absolute number and function of DC occurred in a subset-specific manner during infection. CD8α−CD4+ DC present at B cell follicle borders in the spleen of naive mice were absent 5 days post-Salmonella infection, despite no overall change in the absolute number of CD8α−CD4+ splenic DC. CD8α+ and CD8α−CD4− DC were prominently associated with the red pulp, and the frequency of these cells increased strikingly 5 days post-Salmonella infection. Significant quantitative increases in both CD8α+ and CD8α−CD4− subsets were associated with the in situ redistribution. Examination of Salmonella-infected TAP1−/−/β2-microglobulin−/− mice, which lack CD8α+ T cells, confirmed the differential subset-specific modulations in the DC populations both in situ and quantitatively. Ex vivo intracellular cytokine analysis showed significantly increased frequencies of CD8α+ DC producing TNF-α at days 2 and 5 postinfection. In contrast, CD4+ DC producing TNF-α were transiently increased followed by a significant reduction. No significant increase in IL-12p40 or IL-10 production by splenic DC was detected during the first 5 days post-S. typhimurium infection. Together these data reveal differential modulation of splenic DC subsets with regard to organization, number, and cytokine production during the course of acute Salmonella infection.