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Int J Mol Sci. 2018 Jul 4;19(7). pii: E1959. doi: 10.3390/ijms19071959.

Transmembrane TNF and Partially TNFR1 Regulate TNFR2 Expression and Control Inflammation in Mycobacterial-Induced Pleurisy.

Author information

1
Department of Pathology and Immunology, Centre Medical Universitaire (CMU), Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. uysalhusnu@gmail.com.
2
Department of Pathology and Immunology, Centre Medical Universitaire (CMU), Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. lchavez_galan@iner.gob.mx.
3
Department of Pathology and Immunology, Centre Medical Universitaire (CMU), Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. Marie-Dominique.vesin@unige.ch.
4
Department of Pathology and Immunology, Centre Medical Universitaire (CMU), Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. Guillaume.blaser@unige.ch.
5
Department of Pathology and Immunology, Centre Medical Universitaire (CMU), Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. Mahdia.Benkhoucha@unige.ch.
6
Centre National de la Recherche Scientifique, UMR7355, and Experimental and Molecular Immunology and Neurogenetics, University of Orléans, 45100 Orléans, France. bryffel@cnrs-orleans.fr.
7
Centre National de la Recherche Scientifique, UMR7355, and Experimental and Molecular Immunology and Neurogenetics, University of Orléans, 45100 Orléans, France. quesniaux@cnrs-orleans.fr.
8
Department of Pathology and Immunology, Centre Medical Universitaire (CMU), Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. Irene.Garcia-Gabay@unige.ch.

Abstract

Pleural tuberculosis is one of the most frequent forms of extra-pulmonary tuberculosis observed in patients infected with Mycobacterium tuberculosis. Tumor Necrosis Factor (TNF) is a crucial cytokine needed to control tuberculosis infection that remains a leading cause of morbidity and mortality worldwide. TNF blockade compromises host immunity and may increase the risk of reactivation of latent infection resulting in overt pulmonary, pleural and extra-pulmonary tuberculosis. While TNF signaling is mainly considered pro-inflammatory, its requirement for the anti-inflammation process involved in the resolution of infection and tissue repair is less explored. Our study analyzes the role of TNF and TNF receptors in the control of the inflammatory process associated with Bacillus Calmette-Guérin (BCG)-induced pleurisy. This study shows that the absence of TNF causes exacerbated inflammation in the pleural cavity of BCG-infected mice which is controlled by the transmembrane TNF (tmTNF) expression. The lack of TNF is associated with an impaired cellular expression and shedding of TNFR2 in the pleural cavity. The presence of tmTNF restores the normal expression of TNFR2 on myeloid cells during BCG-induced pleurisy. We also show that absence of TNFR1 affects the expression of TNFR2 on pleural cells and inflammation in the pleural cavity of BCG-infected mice. In conclusion, tmTNF but not soluble TNF prevents pleural cavity inflammation leading to attenuation and the resolution of the inflammatory process caused by mycobacterial pleurisy in association with the expression of TNFR2 on myeloid cells.

KEYWORDS:

BCG-induced pleurisy; TNF; TNF receptors; inflammation

PMID:
29973541
PMCID:
PMC6073837
DOI:
10.3390/ijms19071959
[Indexed for MEDLINE]
Free PMC Article

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