Subclinical infection can be an initiator of inflammaging leading to degenerative disk disease: evidence from host-defense response mechanisms

Eur Spine J. 2021 Sep;30(9):2586-2604. doi: 10.1007/s00586-021-06826-z. Epub 2021 Apr 9.


Purpose: There is considerable controversy on the role of genetics, mechanical and environmental factors, and, recently, on subclinical infection in triggering inflammaging leading to disk degeneration. The present study investigated sequential molecular events in the host, analyzing proteome level changes that will reveal triggering factors of inflammaging and degeneration.

Methods: Ten MRI normal disks (ND) from braindead organ donors and 17 degenerated disks (DD) from surgery were subjected to in-gel-based label-free ESI-LC-MS/MS analysis. Bacterial-responsive host-defense response proteins/pathways leading to Inflammaging were identified and compared between ND and DD.

Results: Out of the 263 well-established host-defense response proteins (HDRPs), 243 proteins were identified, and 64 abundantly expressed HDRPs were analyzed further. Among the 21 HDRPs common to both ND and DD, complement factor 3 (C3) and heparan sulfate proteoglycan 2 (HSPG2) were significantly upregulated, and lysozyme (LYZ), superoxide dismutase 3 (SOD3), phospholipase-A2 (PLA2G2A), and tissue inhibitor of metalloproteinases 3 (TIMP-3) were downregulated in DD. Forty-two specific HDRPs mainly, complement proteins, apolipoproteins, and antimicrobial proteins involved in the complement cascade, neutrophil degranulation, and oxidative-stress regulation pathways representing an ongoing host response to subclinical infection and uncontrolled inflammation were identified in DD. Protein-Protein interaction analysis revealed cross talk between most of the expressed HDRPs, adding evidence to bacterial presence and stimulation of these defense pathways.

Conclusions: The predominance of HDRPs involved in complement cascades, neutrophil degranulation, and oxidative-stress regulation indicated an ongoing infection mediated inflammatory process in DD. Our study has documented increasing evidence for bacteria's role in triggering the innate immune system leading to chronic inflammation and degenerative disk disease.

Keywords: Disk degeneration; Disk proteome; Dysbiosis; Host-defense response proteins; Inflammaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asymptomatic Infections*
  • Chromatography, Liquid
  • Humans
  • Inflammation
  • Tandem Mass Spectrometry*