CD11cHi monocyte-derived macrophages expressing CD38, CD14, and ABCA1 are the dominant niche for Mycobacterium tuberculosis

During tuberculosis, lung myeloid cells have two opposing roles: they are an intracellular niche occupied by Mycobacterium tuberculosis and they restrict bacterial replication. Lung myeloid cells from mice infected with yellow-fluorescent protein expressing M. tuberculosis mice were analyzed by flow cytometry and transcriptional profiling to identify the cell types infected and their response to infection. CD14, CD38, and Abca1 were expressed more highly by infected alveolar macrophages and CD11cHi monocyte-derived macrophages compared to uninfected cells. CD14, CD38, and Abca1 “triple positive” (TP) cells had incomparably high infection rates and bacterial loads, but also a strong interferon-γ signature and nitric oxide synthetase-2 production indicating recognition by T cells. Despite evidence of T cell recognition and appropriate activation, these TP+ macrophages became the dominant niche occupied by M. tuberculosis long-term. Defining this niche should help answer why M. tuberculosis resists elimination from activated macrophages even in the face of T cell immunity. There are two experiments for each myeloid cell subset, and each experiment has three to four replicates. Each replicate represents an individual mouse.