Corynebacterium pyruviciproducens-peptidoglycan: A novel bacterial peptidoglycan inhibiting overexpression of MyD88 in macrophages

Abstract

Objectives: Bacterial peptidoglycan (PGN) is an essential ligand of TLR2 inducing inflammatory damage by boosting MyD88 overexpression in pathogen invasion, such as Methicillin-resistant Staphylococcus aureus (MRSA) infection. CP-PGN is a novel PGN from an adjuvant bacterium, displaying anti-infection immune regulation. This study aimed to clarify the unique moderation of MyD88 expression by CP-PGN. Methods: Compared with other ligands of TLR2, high expression of MyD88 in macrophages was established by MRSA and virus to investigate the immunomodulation of CP-PGN. Results: Compared with PGN derived from MRSA (M-PGN) and chemosynthetic Pam3CSK4 of model agonists of TLR2, CP-PGN could inhibit overexpression of MyD88 in a time- and dose-dependent way in infected macrophages by MRSA or Abelson leukemia virus. CP-PGN also promoted more anti-inflammatory IL-10 and less pro-inflammatory TNF-α in immature primary macrophages. Furthermore, IL-10 secretion induced by CP-PGN was reduced most significantly by blocking the dimer formation of MyD88 with ST2825 and lowering down expression by si-MyD88. Conclusion: CP-PGN could inhibit MyD88 overexpression by infection to moderate inflammatory cytokines. Therefore, CP-PGN is a novel potential ligand of TLR2 to induce inflammatory balance in the process of host defense against invading pathogens.