Impact of Hypoxia-Inducible Factor-1α on Host Immune Metabolism and Tissue Damage During Mycobacterium bovis Infection

HIF-1α is a pivotal regulator of metabolic and inflammatory responses. This study investigated the role of HIF-1α in M. bovis Infection and its effects on host immune metabolism and tissue damage. We evaluated the expression of immunometabolism markers and MMPs infected with M. bovis, and following HIF-1α inhibition in vitro. To understand the implications of HIF-1α inhibition on disease progression, mice at different Infection stages were treated with the HIF-1α Inhibitor, YC-1. Our results revealed an upregulation of the HIF-1α in macrophages post-M. bovis Infection, facilitating enhanced M1 macrophage polarization. The blockade of HIF-1α moderated these responses but escalated MMP activity, hindering Bacterial control. Consistent with our in vitro results, early-stage treatment of mice with YC-1 aggravated pathological alterations and tissue damage, while late-stage HIF-1α inhibition proved beneficial in managing the disease. Overall, our findings underscored the nuanced role of HIF-1α across varying phases of M. bovis Infection.

Mycobacterium bovis; HIF-1α; Immune metabolism; Matrix metalloproteinases; YC-1.