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Open AccessArticle

The Role of Cutibacterium acnes in Intervertebral Disc Inflammation

by Bettina Schmid 1,2, Oliver Hausmann 3,4,5, Wolfgang Hitzl 6,7,8, Yvonne Achermann 5,9,10,† and Karin Wuertz-Kozak 5,11,12,13,*,†
1
Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland
2
Faculty of Science, University of Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland
3
Neuro- and Spine Centre, Klinik St. Anna, St. Anna Street 32, 6006 Lucerne, Switzerland
4
Department of Neurosurgery, Inselspital Berne, University of Berne, Murtenstrasse 11, 3010 Berne, Switzerland
5
CABMM Center for Applied Biotechnology and Molecular Medicine, University of Zurich, 8057 Zurich, Switzerland
6
Research Office (Biostatistics), Paracelsus Medical University, Strubergasse 20, 5020 Salzburg, Austria
7
Research Program Experimental Ophthalmology and Glaucoma Research, Paracelsus Medical University, Müllner Hauptstr. 48, 5020 Salzburg, Austria
8
Department of Ophthalmology and Optometry, Paracelsus Medical University Salzburg, 2020 Salzburg, Austria
9
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
10
Faculty of Medicine, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
11
Department of Biomedical Engineering, Rochester Institute of Technology (RIT), 106 Lomb Memorial Dr., Rochester, NY 14623, USA
12
Institute for Biomechanics, D-HEST, ETH Zurich, Hönggerbergring 64, 8093 Zurich, Switzerland
13
Spine Center, Schön Clinic Munich Harlaching (Academic Teaching Hospital and Spine Research Institute of the Paracelsus Medical University Salzburg), Harlachinger Str. 51, 81547 Munich, Germany
*
Author to whom correspondence should be addressed.
The authors contributed equally to this manuscript.
Biomedicines 2020, 8(7), 186; https://doi.org/10.3390/biomedicines8070186
Received: 28 May 2020 / Revised: 24 June 2020 / Accepted: 26 June 2020 / Published: 30 June 2020
Recently, the role of infection of the intervertebral disc (IVD) with Cutibacterium acnes (C. acnes) as a contributor to disc-related low back pain (LBP) has been discussed. The aim of this study was to investigate whether and how C. acnes contributes to the inflammatory processes during IVD disease. The prevalence of C. acnes infection in human IVD tissue was determined by aerobic and anaerobic culture. Thereafter, primary human IVD cells were infected with a reference and a clinical C. acnes strain and analyzed for pro-inflammatory markers (gene/protein level). In a subsequent experiment, the involvement of the Toll-like receptor (TLR) pathway was investigated by co-treatment with sparstolonin B, a TLR2/4 inhibitor. We detected C. acnes in 10% of IVD biopsies (with either herniation or degeneration). Stimulating IVD cells with both C. acnes strains strongly and significantly upregulated expression of Interleukin (IL)-1β, IL-6, IL-8, and inducible nitric oxide synthase (iNOS). IL-6, cyclooxygenase (COX)-2, and iNOS expression was reduced upon TLR2/4 inhibition in 3 out of 5 donors, whereby responders and non-responders could not be differentiated by their basal TLR2 or TLR4 expression levels. We demonstrate that exposure of IVD cells to C. acnes induces an inflammatory response that may contribute to the development of discogenic LBP by involving TLR2/4 activation, yet only in a subgroup of patients. Whether the same response will be observed in vivo and where lower inoculums are present remains to be proven in future studies. View Full-Text
Keywords: Cutibacterium acnes; Toll-like receptor 2 (TLR2); Toll-like receptor 4 (TLR4); interleukin; low back pain; discogenic back pain; pro-inflammatory cytokines; responders; non-responders Cutibacterium acnes; Toll-like receptor 2 (TLR2); Toll-like receptor 4 (TLR4); interleukin; low back pain; discogenic back pain; pro-inflammatory cytokines; responders; non-responders
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MDPI and ACS Style

Schmid, B.; Hausmann, O.; Hitzl, W.; Achermann, Y.; Wuertz-Kozak, K. The Role of Cutibacterium acnes in Intervertebral Disc Inflammation. Biomedicines 2020, 8, 186.

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