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

Rasmus Mortensen; Helena Strand Clemmensen; Joshua S. Woodworth; Marie Louise Therkelsen; Tehmina Mustafa; Kristian Tonby; Synne Jenum; Else Marie Agger; Anne Ma Dyrhol-Riise; Peter Andersen

doi:10.1038/s42003-019-0530-3

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

Rasmus Mortensen^*, Helena Strand Clemmensen, Joshua S. Woodworth, Marie Louise Therkelsen, Tehmina Mustafa, Kristian Tonby, Synne Jenum, Else Marie Agger, Anne Ma Dyrhol-Riise, Peter Andersen

^*Corresponding author for this work

10 Citations (Scopus)

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Abstract

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.

Original language	English
Article number	288
Journal	Communications Biology
Volume	2
Issue number	1
Number of pages	10
DOIs	https://doi.org/10.1038/s42003-019-0530-3
Publication status	Published - 2019

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Cyclooxygenase inhibitors impair CD4 T cell immunity and exacerbate Mycobacterium tuberculosis infection in aerosol-challenged miceFinal published version, 1.12 MBLicence: CC BY

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Mortensen, R., Clemmensen, H. S., Woodworth, J. S., Therkelsen, M. L., Mustafa, T., Tonby, K., Jenum, S., Agger, E. M., Dyrhol-Riise, A. M., & Andersen, P. (2019). Cyclooxygenase inhibitors impair CD4 T cell immunity and exacerbate Mycobacterium tuberculosis infection in aerosol-challenged mice. Communications Biology, 2(1), Article 288. https://doi.org/10.1038/s42003-019-0530-3

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

abstract = "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.",

author = "Rasmus Mortensen and Clemmensen, {Helena Strand} and Woodworth, {Joshua S.} and Therkelsen, {Marie Louise} and Tehmina Mustafa and Kristian Tonby and Synne Jenum and Agger, {Else Marie} and Dyrhol-Riise, {Anne Ma} and Peter Andersen",

year = "2019",

doi = "10.1038/s42003-019-0530-3",

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T1 - Cyclooxygenase inhibitors impair CD4 T cell immunity and exacerbate Mycobacterium tuberculosis infection in aerosol-challenged mice

AU - Mortensen, Rasmus

AU - Clemmensen, Helena Strand

AU - Woodworth, Joshua S.

AU - Therkelsen, Marie Louise

AU - Mustafa, Tehmina

AU - Tonby, Kristian

AU - Jenum, Synne

AU - Agger, Else Marie

AU - Dyrhol-Riise, Anne Ma

AU - Andersen, Peter

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1038/s42003-019-0530-3

DO - 10.1038/s42003-019-0530-3

M3 - Journal article

C2 - 31396568

AN - SCOPUS:85071176401

SN - 2399-3642

VL - 2

JO - Communications Biology

JF - Communications Biology

IS - 1

M1 - 288

ER -

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

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