Mycobacteria Exploit Host GPR84 to Dampen Pro-Inflammatory Responses and Promote Infection in Macrophages.

Tuberculosis (TB) remains the major cause of mortality and morbidity, causing approximately 1.3 million deaths annually. As a highly successful pathogen, () has evolved numerous strategies to evade host immune responses, making it essential to understand the interactions between and host cells. G-protein-coupled receptor 84 (GPR84), a member of the G-protein-coupled receptor family, contributes to the regulation of pro-inflammatory reactions and the migration of innate immune cells, such as macrophages. Its role in mycobacterial infection, however, has not yet been explored. We found that GPR84 is induced in whole blood samples from tuberculosis patients and )-infected macrophage models. Using a infection model in mouse tails, we found that GPR84 is an important determinant of the extent of tissue damage. Furthermore, from our studies in an in vitro macrophage infection model, it appears that GPR84 inhibits pro-inflammatory cytokines expression and increases intracellular lipid droplet (LD) accumulation, thereby promoting intracellular bacterial survival. Our findings suggest that GPR84 could be a potential therapeutic target for host-directed anti-TB therapeutics.