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Publication : Cyclooxygenase inhibitors impair CD4 T cell immunity and exacerbate <i>Mycobacterium tuberculosis</i> infection in aerosol-challenged mice.

First Author  Mortensen R Year  2019
Journal  Commun Biol Volume  2
Pages  288 PubMed ID  31396568
Mgi Jnum  J:278084 Mgi Id  MGI:6356155
Doi  10.1038/s42003-019-0530-3 Citation  Mortensen R, et al. (2019) Cyclooxygenase inhibitors impair CD4 T cell immunity and exacerbate Mycobacterium tuberculosis infection in aerosol-challenged mice. Commun Biol 2:288
abstractText  Tuberculosis, caused by infection with Mycobacterium tuberculosis (Mtb), kills over 1.6 million people each year despite availability of antibiotics. The increase in drug resistant Mtb strains is a major public health emergency and host-directed therapy as adjunct to antibiotic treatment has gained increased interest. Cyclooxygenase inhibitors (COXi) are frequently used drugs to alleviate tuberculosis related symptoms. Mouse studies of acute intravenous Mtb infection have suggested a potential benefit of COXi for host-directed therapy. Here we show that COXi treatment (ibuprofen and celecoxib) is detrimental to Mtb control in different mouse models of respiratory infection. This effect links to impairments of the Type-1 helper (Th1) T-cell response as CD4 T-cells in COXi-treated animals have significantly decreased Th1 differentiation, reduced IFNgamma expression and decreased protective capacity upon adoptive transfer. If confirmed in clinical trials, these findings could have major impact on global health and question the use of COXi for host-directed therapy.
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