Temporal control of macrophage pro-inflammatory phenotype by a biphasic HIF-1α regulatory program.

HIF-1α rapidly activates in macrophages via a ROS circuit, driving early glycolysis, cytokine production, and bacterial killing within hours of stimulation.

• Why it matters: Understanding how macrophages initiate inflammatory responses is crucial for developing therapies for infections and inflammatory diseases, but the early regulatory mechanisms remain unclear.
• What they did: The study used molecular and cellular approaches to show that HIF-1α is activated shortly after stimulation through a RUBCN-NOX2 ROS pathway, influencing metabolic and immune functions.
• The result: This reveals a biphasic HIF-1α program that temporally coordinates redox signaling with metabolic and antimicrobial responses, offering insights into early macrophage activation and potential intervention points.