Human Macrophages Secrete Both Interferon α and Interferon β Proteins During Infection with Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) infection activates type I interferons (IFNs), which are crucial mediators of tuberculosis pathogenesis. Despite assumptions that IFNα and IFNβ are secreted by human macrophages, direct protein quantification in primary monocyte-derived macrophages (MDMs) 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 postinfection, 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 provide a foundation for exploring their role in host–pathogen interactions.