Type I interferons in tuberculosis pathogenesis and prevention

Type I IFNs have traditionally been categorized as pathogenic in Mtb infections, but accumulating evidence points to a key protective function for these cytokines, specifically during Mtb vaccination. 

Complex interactions and dynamics resulting from them, during Mtb infection, can lead to fluctuating levels of Type I and II IFNs that are mostly correlated with disease prognosis, but the potential mechanisms underlying these changes remain unclear.

ISG15, which is upregulated by Type I IFN signaling, provides one of many potential resolutions to the interferon dilemma by linking initial Type I signaling followed by later Type II signaling via protein–protein interactions.

Performing tuberculosis (TB) studies in models which faithfully recapitulate the heterogeneity of human Mtb infection, particularly the structure and function of TB granulomas, for example, macaques, would likely enhance our understanding of how Type I IFNs contribute to protection from TB, and why dysregulated Type I IFN signaling can promote TB pathology.

https://www.cell.com/trends/microbiology/fulltext/S0966-842X(25)00329-4

https://sciencemission.com/Type-I-interferons-in-tb-pathogenesis-and-prevention