Cyclooxygenase inhibitors impair CD4 T cell immunity and exacerbate Mycobacterium tuberculosis infection in aerosol-challenged mice

• Published in: Communications biology Vol. 2; no. 1; p. 288
• Main Authors: Mortensen, Rasmus, Clemmensen, Helena Strand, Woodworth, Joshua S., Therkelsen, Marie Louise, Mustafa, Tehmina, Tonby, Kristian, Jenum, Synne, Agger, Else Marie, Dyrhol-Riise, Anne Ma, Andersen, Peter
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 2019; Nature Publishing Group
• Subjects: 13/21; 13/31; 13/51; 631/250/255/1856; 631/326/41; 64/110; 64/60; 692/699/255/1856; Adaptive immunity; Adoptive Transfer; Aerosols; Animal models; Animals; Antibiotics; Bacterial Load; Biology; Biomedical and Life Sciences; CD4 antigen; Celecoxib; Celecoxib - toxicity; Cell differentiation; Cell Differentiation - drug effects; Clinical trials; Cyclooxygenase 2 Inhibitors - toxicity; Cyclooxygenase Inhibitors - toxicity; Disease Models, Animal; Disease Progression; Drug resistance; Female; Helper cells; Host-Pathogen Interactions; Ibuprofen; Ibuprofen - toxicity; Infections; Inhalation Exposure; Interferon-gamma - immunology; Intravenous administration; Life Sciences; Lung - drug effects; Lung - immunology; Lung - microbiology; Lymphocyte Activation - drug effects; Lymphocytes T; Mice, Inbred C3H; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; Mycobacterium tuberculosis - pathogenicity; Prostaglandin endoperoxide synthase; Public health; Respiratory tract infection; Th1 Cells - drug effects; Th1 Cells - immunology; Th1 Cells - microbiology; Th1 Cells - transplantation; Tuberculosis; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - microbiology; γ-Interferon; Bacteria; Tuberculosis
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-019-0530-3

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 IFNγ 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. Rasmus Mortensen et al. examine the effects of cyclooxygenase inhibitors in an aerosol Mycobacterium tuberculosis infection mouse model. They find that the treatment diminish bacterial control and impairs adaptive immunity by reducing the differentiation of CD4 T-cells into Type 1 T helper cells.