Summary
Infection-induced thrombocytosis is a clinically important complication of tuberculosis infection. Recent studies have highlighted the utility of aspirin as a host-directed therapy modulating the inflammatory response to infection, but have not investigated the possibility that the effect of aspirin is related to an anti-platelet mode of action. Here we utilise the zebrafish-Mycobacterium marinum model to show mycobacteria drive host haemostasis through the formation of granulomas. Treatment of infected zebrafish with aspirin markedly reduced mycobacterial burden. This effect is reproduced by treatment with platelet-specific glycoprotein IIb/IIIa inhibitors demonstrating a detrimental role for infection-induced thrombocytosis. We find that the reduction in mycobacterial burden is dependent on macrophages and granuloma formation. Our study identifies haemostasis as a novel virulence mechanism of pathogenic mycobacteria and provides evidence of platelet activation as an efficacious target of aspirin, a widely available and affordable host-directed therapy candidate for tuberculosis.