The Role of Cutibacterium acnes in Intervertebral Disc Inflammation.

Bettina Schmid,Oliver Hausmann,Yvonne Achermann,Wolfgang Hitzl,Karin Wuertz-Kozak

doi:10.3390/biomedicines8070186

Abstract

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.

Highlights

Low back pain (LBP) is the primary cause of disability worldwide, with a lifetime prevalence of>80% [1]
We demonstrate that exposure of intervertebral disc (IVD) cells to C. acnes induces an inflammatory response that may contribute to the development of discogenic low back pain (LBP) by involving
The biopsies with detection of C. acnes originated from two patients with disc herniation (DH) and from one with disc degeneration (DD)

Summary

Introduction

Low back pain (LBP) is the primary cause of disability worldwide, with a lifetime prevalence of>80% [1]. While degeneration of the IVD is a process that is required for DH, it does not necessarily lead to DH, but may be limited to, e.g., microfissures in the endplate or the AF In both cases, inflammatory processes are known to play a crucial role in pain development. IVD cells themselves can release such pro-inflammatory cytokines [5] This is relevant in painful DD, where nociception is strongly associated with innervation as well as with the occurrence of chronic inflammation within the tissue, with selected pro-inflammatory cytokines (e.g., IL-6) causing direct nerve irritation [7,8,9]. Several receptors and pathways seem to be implicated in IVD inflammation, such as Toll-like receptors (TLRs), which can be activated by so-called damage-associated molecular patterns (DAMPs)) as well as the NF-kB and MAPK pathways [10,11,12,13]

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