Impact of Hypoxia-Inducible Factor-1α on Host Immune Metabolism and Tissue Damage During Mycobacterium bovis Infection.
J Infect Dis
; 2024 Jun 06.
Article
de En
| MEDLINE
| ID: mdl-38843067
ABSTRACT
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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Langue:
En
Journal:
J Infect Dis
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine
Pays de publication:
États-Unis d'Amérique