Abstract
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 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 cells compared to uninfected cells. CD14, CD38, and Abca1 "triple positive" (TP) cells had not only the highest 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 are a cellular compartment occupied by M. tuberculosis long-term. Defining the niche where M. tuberculosis resists elimination promises to provide insight into why inducing sterilizing immunity is a formidable challenge.
Highlights
Our respiratory system is in direct contact with the environment and the lung’s large surface area is patrolled by the immune system to eliminate inhaled particles and microbes
The initial cell type infected by Mycobacterium tuberculosis is generally acknowledged to be the alveolar macrophage; subsequently, the bacilli spread to other types of myeloid cells, and other macrophages, dendritic cells, and neutrophils become infected
How M. tuberculosis persists despite a robust immune response is a critical question
Summary
Our respiratory system is in direct contact with the environment and the lung’s large surface area is patrolled by the immune system to eliminate inhaled particles and microbes. To understand the pathogenesis of these and other diseases, great effort has gone into characterizing the lung’s resident myeloid cells [1, 2]. Resident cells change phenotype, function, and location, while other cells are recruited and marginate from the blood to enter lung tissue [3, 4]. Myeloid cells have enormous plasticity and their activation states and functions are shaped by exogenous signals to which they are exposed (e.g., bacterial products, cytokines, hypoxia, cigarette smoke) [5,6,7,8]. The same cell type can be pro-inflammatory and resist infection, or anti-inflammatory and help resolve inflammation and remodel injured tissue
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