Type 1 diabetes alters early macrophage-Mycobacterium tuberculosis transcriptional coordination during infection

Diabetes mellitus is a risk factor for tuberculosis, but the underlying mechanisms remain unclear. We examined the host-Mycobacterium tuberculosis (Mtb) interaction in diabetes. Monocyte-derived macrophages from people with type 1 diabetes and healthy controls were infected with Mtb, and analyzed for host and Mtb gene expression and culture supernatant cytokines. Expression of antibacterial defense genes upon infection was mostly similar, but IFN-γ, both at RNA and protein level, was lower in macrophages from people with diabetes. Intracellular Mtb showed stress responses and a metabolic shutdown, both in macrophages from people with diabetes and controls. Expression of CYBB and other Mendelian susceptibility to mycobacterial disease genes strongly correlated with expression of Mtb cell wall and lipid genes in control macrophages, but much less so in diabetes. This rich dual RNA-seq dataset shows how type 1 diabetes may affect cross-talk between macrophages and Mtb, providing a valuable resource for future mechanistic studies.