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Background  Tuberculosis (TB) causes a major burden on global health with long and cumbersome TB treatment regimens. Host-directed immune modulating therapies have been suggested as adjunctive treatment to TB antibiotics. Upregulated cyclooxygenase-2 (COX-2)-prostaglandin E2 (PGE2) signaling pathway may cause a dysfunctional immune response that favors survival and replication of  Mycobacterium tuberculosis (Mtb) .    Methods  Blood samples were obtained from patients with latent TB ( n  = 9) and active TB ( n  = 33) before initiation of anti-TB chemotherapy. COX-2 expression in monocytes and ESAT-6 and Ag85 specific T cell cytokine responses (TNF-α, IFN-γ, IL-2), proliferation (carboxyfluorescein succinimidyl ester staining) and regulation (FOXP3+ T regulatory cells) were analysed by flow cytometry and the in vitro effects of the COX-1/2 inhibitor indomethacin were measured.    Results  We demonstrate that indomethacin significantly down-regulates the fraction of  Mtb  specific FOXP3+ T regulatory cells (ESAT-6;  p  = 0.004 and Ag85;  p  < 0.001) with a concomitant reduction of  Mtb  specific cytokine responses and T cell proliferation in active TB. Although active TB tend to have higher levels, there are no significant differences in COX-2 expression between unstimulated monocytes from patients with active TB compared to latent infection. Monocytes in both TB groups respond with a significant upregulation of COX-2 after in vitro stimulation.    Conclusions  Taken together, our in vitro data indicate a modulation of the Th1 effector and T regulatory cells in  Mtb  infection in response to the COX-1/2 inhibitor indomethacin. The potential role as adjunctive host-directed therapy in TB disease should be further evaluated in both animal studies and in human clinical trials.

The COX- inhibitor indomethacin reduces Th1 effector and T regulatory cells in vitro in Mycobacterium tuberculosis infection