Dendritic cell depletion and repopulation in the lung after irradiation and bone marrow transplantation in mice

Abstract

Macrophages and dendritic cells are essential for innate and adaptive immunity, respectively and have been reported to exhibit variable radiosensitivities in response to irradiation in various bone marrow transplantation (BMT) protocols. In order to address this controversy, we analyzed the magnitude of depletion and repopulation of both “conventional“ CD11bpos DC and CD103pos DC subsets as well as different pulmonary macrophage subsets in the lung tissue in response to irradiation and BMT in a mouse model. In our study, CD45.2pos donor bone marrow cells were transplanted into irradiated CD45.1pos recipient mice, in order to examine the depletion of recipient-type and the repopulation of donor-type DC and macrophage subsets. We observed an apoptosis- and necrosis-mediated >90% depletion of the recipient CD103pos DC subset and only a 50–60% depletion of recipient CD11bpos DC from lung parenchymal tissue at day 3 and 5, whereas recipient alveolar and lung macrophages were much less radiosensitive, showing ˜50% depletion by days 14–21 post-treatment. Complete repopulation of lung tissue with donor DC subsets was observed by days 10 and 28 for CD11bpos DC and CD103pos DC, whereas alveolar and lung macrophages were repopulated by 6 and 10 weeks post-treatment. Furthermore, infection of mice with S. pneumoniae highly accelerated the turnover of lung DC as well as lung macrophage subsets. Our data illustrate the vulnerability of lung CD103pos DC and CD11bpos DC to irradiation and indicate an accelerated turnover of lung DC subsets relative to pulmonary macrophages. Our findings may have important implications for the development of adjuvant immune-stimulatory protocols which could reduce the risk of opportunistic infections in patients undergoing BMT.