Time course of mycobacterial infection of dendritic cells in the lungs of intranasally infected mice.

Setting: Dendritic cells (DC) could regulate between the protective and pathogenic immune responses following tuberculous infection. In this paper we investigated if their early infection in the lungs represents a plausible alternative to cross-priming with mycobacterial antigens acquired from infected macrophages. Objective: To determine the extent and time course of infection of lung DCs following intranasal inoculation of BALB/c mice with green fluorescent protein (GFP) tagged Bacillus Calmette-Guerin (BCG). Results: A fraction of GFP-BCG infected lung cells were classified as monocytic DCs with the CD11c(+)IA(+)33D1(+)CD8a(-) phenotype. These cells represented 5-18% of the total GFP(+) cells, the bulk of which were macrophages. The infected DCs could be separated by cell size into two fractions with similar cell surface staining properties during the 2-72 h period after infection. An unexpected difference was observed for the time course of infection between DCs and macrophages: DC infection peaked at 48h followed by decline at 72h, while the proportion of infected macrophages remained steady during the same period. Conclusion: The presented results are direct evidence that monocytic DCs are recruited to the lungs and take up live bacilli within 48 h of intranasal infection with GFP-BCG. This finding is pertinent for the regulation of pulmonary and systemic immune responses and possibly for the dissemination of mycobacterial infection by DCs. (C)