Cutting edge: TNF is essential for mycobacteria-induced MINCLE expression, macrophage activation, and Th17 adjuvanticity

Schick J, Schäfer J, Alexander C, Dichtl S, Murray PJ, Christensen D, Sorg U, Pfeffer K, Schleicher U, Lang R (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Journal of Immunology American Association of Immunologists

Book Volume: 205

Pages Range: 323-328

Journal Issue: 2

DOI: 10.4049/jimmunol.2000420

Abstract

TNF blockade is a successful treatment for human autoimmune disorders like rheumatoid arthritis and inflammatory bowel disease yet increases susceptibility to tuberculosis and other infections. The C-type lectin receptors (CLR) MINCLE, MCL, and DECTIN-2 are expressed on myeloid cells and sense mycobacterial cell wall glycolipids. In this study, we show that TNF is sufficient to upregulate MINCLE, MCL, and DECTIN-2 in macrophages. TNF signaling through TNFR1 p55 was required for upregulation of these CLR and for cytokine secretion in macrophages stimulated with the MINCLE ligand trehalose-6,6-dibehenate or infected with Mycobacterium bovis bacillus Calmette-Guérin. The Th17 response to immunization with the MINCLE dependent adjuvant trehalose-6,6-dibehenate was specifically abrogated in TNF-deficient mice and strongly attenuated by TNF blockade with etanercept. Together, interference with production or signaling of TNF antagonized the expression of DECTIN-2 family CLR, thwarting vaccine responses and possibly increasing infection risk.

Authors with CRIS profile

Johanna Winkelmann Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Ulrike Schleicher Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Roland Lang Professur für Angeborene Immunität und Pathogenerkennung

Involved external institutions

Forschungszentrum Borstel - Leibniz-Zentrum für Medizin und Biowissenschaften / Research Center Borstel - Leibniz-Center for Medicine and Biosciences DE Germany (DE) Statens Serum Institut DK Denmark (DK) Heinrich-Heine-Universität Düsseldorf DE Germany (DE) Max-Planck-Institut für Biochemie / Max Planck Institute of Biochemistry DE Germany (DE)

How to cite

APA:

Schick, J., Schäfer, J., Alexander, C., Dichtl, S., Murray, P.J., Christensen, D.,... Lang, R. (2020). Cutting edge: TNF is essential for mycobacteria-induced MINCLE expression, macrophage activation, and Th17 adjuvanticity. Journal of Immunology, 205(2), 323-328. https://doi.org/10.4049/jimmunol.2000420

MLA:

Schick, Judith, et al. "Cutting edge: TNF is essential for mycobacteria-induced MINCLE expression, macrophage activation, and Th17 adjuvanticity." Journal of Immunology 205.2 (2020): 323-328.

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