Pro-inflammatory and neurotrophic factor responses of cells derived from degenerative human intervertebral discs to the opportunistic pathogen Cutibacterium acnes

Manu N Capoor, Anna Konieczna, Andrew McDowell, Filip Ruzicka, Martin Smrcka, Radim Jancalek, Karel Maca, Michael Lujc, Fahad S. Ahmed, Christof Birkenmaier, Stefan Dudli, Ondrej Slaby

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Abstract

Previously, we proposed the hypothesis that similarities in the inflammatory response observed in acne vulgaris and degenerative disc disease (DDD), especially the central role of interleukin (IL)-1β, may be further evidence of the role of the anaerobic bacterium Cutibacterium (previously Propionibacterium) acnes in the underlying aetiology of disc degeneration. To investigate this, we examined the upregulation of IL-1β, and other known IL-1β-induced inflammatory markers and neurotrophic factors, from nucleus-pulposus-derived disc cells infected in vitro with C. acnes for up to 48 h. Upon infection, significant upregulation of IL-1β, alongside IL-6, IL-8, chemokine (C-C motif) ligand 3 (CCL3), chemokine (C-C motif) ligand 4 (CCL4), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), was observed with cells isolated from the degenerative discs of eight patients versus non-infected controls. Expression levels did, however, depend on gene target, multiplicity and period of infection and, notably, donor response. Pre-treatment of cells with clindamycin prior to infection significantly reduced the production of pro-inflammatory mediators. This study confirms that C. acnes can stimulate the expression of IL-1β and other host molecules previously associated with pathological changes in disc tissue, including neo-innervation. While still controversial, the role of C. acnes in DDD remains biologically credible, and its ability to cause disease likely reflects a combination of factors, particularly individualised response to infection.
Original languageEnglish
Pages (from-to)1-16
Number of pages16
JournalInternational Journal of Molecular Sciences
Volume22
Issue number2347
DOIs
Publication statusPublished - 26 Feb 2021

Keywords

  • Cutibacterium acnes; disc cells; co-culture; inflammation; neurotrophic factors; gene expression; intracellular

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