TLR2 and the NLRP3 inflammasome mediate IL-1β production in Prevotella nigrescens-infected dendritic cells

Int J Med Sci. 2021 Jan 1;18(2):432-440. doi: 10.7150/ijms.47197. eCollection 2021.

Abstract

Prevotella nigrescens is an oral pathogen that is frequently observed in the subgingival plaque of periodontitis patients. Interleukin-1β (IL-1β) is known to be involved in the immunopathology of periodontal diseases and has been implicated in the destruction of bone. In this study, we investigated the mechanism of IL-1β production by P. nigrescens in murine bone marrow-derived dendritic cells (BMDCs). Our results showed that a host receptor, Toll-like receptor 2 (TLR2), but not TLR4 is required for pro-IL-1β induction and nucleotide-binding oligomerization domain like receptor pyrin domain containing 3 (NLRP3) priming in BMDCs in response to P. nigrescens and activation of the NLRP3 inflammasome is necessary for processing of pro-IL-1β into mature IL-1β. In addition, an inhibitor assay revealed that production of reactive oxygen species, P2X7R activity, and release of cathepsin B are involved in IL-1β production in BMDCs in response to P. nigrescens.

Keywords: BMDCs; IL-1β; NLRP3 inflammasome; Prevotella nigrescens; TLR2.

MeSH terms

  • Animals
  • Cathepsin B / metabolism
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Gram-Negative Bacterial Infections / immunology*
  • Gram-Negative Bacterial Infections / microbiology
  • Humans
  • Inflammasomes / immunology
  • Inflammasomes / metabolism
  • Interleukin-1beta / metabolism*
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Periodontitis / immunology*
  • Periodontitis / microbiology
  • Prevotella nigrescens / immunology*
  • Primary Cell Culture
  • Reactive Oxygen Species / metabolism
  • Receptors, Purinergic P2X7 / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism*

Substances

  • IL1B protein, mouse
  • Inflammasomes
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • P2rx7 protein, mouse
  • Reactive Oxygen Species
  • Receptors, Purinergic P2X7
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Cathepsin B
  • Ctsb protein, mouse