Human macrophages secrete both interferon α and interferon β protein during infection with Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) infection activates type I interferons (IFNs) which are crucial mediators of tuberculosis (TB) pathogenesis. Despite assumptions that IFNα and IFNβ are secreted by macrophages, direct protein quantification in primary human monocyte-derived macrophages is surprisingly lacking. Here, we demonstrate measurable IFNα and IFNβ secretion by MDMs infected with both virulent (H37Rv) and attenuated (H37Ra) Mtb strains as early as 48 h post-infection, with levels persisting at 120 h. These findings challenge existing assumptions about type I IFN kinetics and highlight the importance of timing in experimental designs and provides a foundation for exploring their role in host-pathogen interactions.