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

• Published in: Tuberculosis (Edinburgh, Scotland) Scotland), 2005-01, Vol.85 (1), p.81-88
• Main Authors: Reljic, R., Di Sano, C., Crawford, C., Dieli, F., Challacombe, S., Ivanyi, J.
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Animals; Antigens, Bacterial - immunology; Antigens, CD - immunology; Antigens, Surface - immunology; BCG Vaccine - administration & dosage; Cell Size; Dendritic cells; Dendritic Cells - immunology; Green Fluorescent Proteins; Luminescent Agents; Lung; Lung - microbiology; Lung - pathology; Macrophages - immunology; Mice; Mice, Inbred BALB C; Monocytes - immunology; Mycobacteria; Mycobacterium Infections - immunology; Mycobacterium Infections - pathology; Rodent; Time Factors; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - pathology
• ISSN: 1472-9792; 1873-281X
• DOI: 10.1016/j.tube.2004.09.006

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 48 h followed by decline at 72 h, 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.