Characterization of AIM2 expression in human macrophages during M. tuberculosis infection

Abstract

Abstract Tuberculosis (TB) is a leading contributor to global mortality and is a well-known threat to global health. The disease-causing bacterium, Mycobacterium tuberculosis (M.tb), has demonstrated resistance to current treatments, thus necessitating novel methods to fight the disease. The investigation of host-bacterium interactions may provide insight for development of effective host-directed therapies, thus circumventing antibiotic resistance. The body’s defense system against airborne M.tb includes alveolar macrophages (AMs) responsible for elimination of foreign agents. However, they do not effectively eliminate M.tb, leading to bacterial propagation. It was previously found that the NOD-like receptor, absent in melanoma 2 (AIM2), plays key roles in M.tb infection in murine macrophages. However, the expression of AIM2 in primary human cells during M.tb infection remains unknown. To this end, we characterized AIM2 expression in human monocyte-derived macrophages (MDMs) and AMs during M.tb infection via quantitative real-time PCR (qRT-PCR). We found that M.tb induces AIM2 transcripts in human MDMs and AMs, in a time-dependent manner. We also investigated the contribution of peroxisome proliferator-activated receptor (PPAR)γ to AIM2 expression due to its known regulation of several genes involved in the human macrophage response to M.tb. We found that PPARγ mediates AIM2 expression. In conclusion, the increased AIM2 gene expression observed in MDMs and AMs during M.tb infection necessitates further investigation into its function and its potential use as a target for M.tb host-directed therapy.