Coenzyme A activates TLR4 and enhances alternative macrophage activation in line with MyD88 agonism.

Exogenous CoA acts as a weak TLR4 agonist that enhances IL-4 driven macrophage activation via MyD88 in vitro and in vivo.

• Why it matters: Understanding how metabolites influence immune responses can reveal new pathways for controlling inflammation and tissue repair, addressing gaps in the mechanisms of immune modulation.
• What they did: The study examined CoA's effect on macrophages, finding that perturbations in intracellular CoA do not affect M(IL-4) differentiation, but exogenous CoA primes macrophages through TLR4 and MyD88 signaling.
• The result: CoA's activation of TLR4 increases macrophage responsiveness to IL-4, promoting alternative activation and inflammation resolution, suggesting DAMPs can prime macrophages for tissue repair.