The Role of Dendritic Cell Subsets in the Early Immune Response to Mycobacterial Infection

Abstract

The early immune response to tuberculosis (TB) is poorly understood. However, recent evidence has shown that dendritic cells (DC) are important for both control of bacterial growth and for activating adaptive immunity. DC are divided into functionally and phenotypically distinct subsets, but the role of each of these subsets in the early immune response to tuberculosis remains unknown. This study aimed to investigate the roles of DC subsets in a murine model of mycobacterial infection. Use of a fluorescent strain of the attenuated TB vaccine strain Mycobacterium bovis BCG, combined with multicolour flow cytometry, enabled detection of BCG associated DC subsets within the murine lung during the first 14 days of infection. The early immune response to mycobacterial infection was found to be highly dynamic, with significant variation in the proportion of BCG associated cells in each DC subset of the lung during infection. CD11b+ conventional DC (cDC) and plasmacytoid DC (pDC) were found to be associated with BCG during the first 14 days of infection, whereas CD103+ cDC were not. Differential expression of the cell surface markers GR-1, CD11b and CD11c detected within previously described DC subsets correlated with their propensity to associate with BCG. Conventional DC and pDC were found to respond differently to mycobacterial infection; cDC upregulated expression of CD86 during infection whereas pDC were found to do the opposite, suggesting that these subsets have distinct roles during early infection. Importantly, and contrary to current dogma, alveolar macrophages were not found to associate with BCG during early infection. This study highlights the distinct roles of different DC subsets during mycobacterial infection. This research may have implications for the development of a novel vaccine or therapy for tuberculosis, for which there is a significant need.