The orphan receptor GPR84 drives inflammation in Buruli ulcer development

expression through Toll-like receptor 2 engagement, promoting proinflammatory cytokine release through a self-amplifying loop that sustained receptor expression and inflammatory signaling. Moreover, pharmacological inhibition of GPR84 with the antagonist PBI-4050, in combination with antibiotics, accelerated tissue repair in infected GPR84-competent mice, which was associated with attenuation of inflammatory responses. Together, these findings establish GPR84 as a promising target for host-directed therapeutic interventions in Buruli ulcer and its expression as a potential biomarker of lesion activity.