Infection Rate and Tissue Localization of Murine IL-12p40-Producing Monocyte-Derived CD103(+) Lung Dendritic Cells during Pulmonary Tuberculosis
2013 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 8, no 7, e69287- p.Article in journal (Refereed) Published
Non-hematopoietic cells, including lung epithelial cells, influence host immune responses. By co-culturing primary alveolar epithelial cells and monocytes from naive donor mice, we show that alveolar epithelial cells support monocyte survival and differentiation in vitro, suggesting a role for non-hematopoietic cells in monocyte differentiation during the steady state in vivo. CD103(+) dendritic cells (alpha E-DC) are present at mucosal surfaces. Using a murine primary monocyte adoptive transfer model, we demonstrate that alpha E-DC in the lungs and pulmonary lymph nodes are monocyte-derived during pulmonary tuberculosis. The tissue localization may influence the functional potential of alpha E-DC that accumulate in Mycobacterium tuberculosis-infected lungs. Here, we confirm the localization of alpha E-DC in uninfected mice beneath the bronchial epithelial cell layer and near the vascular wall, and show that alpha E-DC have a similar distribution in the lungs during pulmonary tuberculosis and are detected in the bronchoalveolar lavage fluid from infected mice. Lung DC can be targeted by M. tuberculosis in vivo and play a role in bacterial dissemination to the draining lymph node. In contrast to other DC subsets, only a fraction of lung alpha E-DC are infected with the bacterium. We also show that virulent M. tuberculosis does not significantly alter cell surface expression levels of MHC class II on infected cells in vivo and that alpha E-DC contain the highest frequency of IL-12p40(+) cells among the myeloid cell subsets in infected lungs. Our results support a model in which inflammatory monocytes are recruited into the M. tuberculosis-infected lung tissue and, depending on which non-hematopoietic cells they interact with, differentiate along different paths to give rise to multiple monocyte-derived cells, including DC with a distinctive alpha E-DC phenotype.
Place, publisher, year, edition, pages
2013. Vol. 8, no 7, e69287- p.
IdentifiersURN: urn:nbn:se:su:diva-93776DOI: 10.1371/journal.pone.0069287ISI: 000321692000041OAI: oai:DiVA.org:su-93776DiVA: diva2:649413
FunderSwedish Research Council, K2007-57X-20360-01-4Swedish Heart Lung Foundation