TLR-2 neutralization potentiates microglial M1 to M2 switching by the combinatorial treatment of ciprofloxacin and dexamethasone during S. aureus infection

J Neuroimmunol. 2020 Jul 15:344:577262. doi: 10.1016/j.jneuroim.2020.577262. Epub 2020 May 12.

Abstract

Microglial inflammation plays a pivotal role in the pathogenesis of S. aureus induced brain abscesses. The objective of this study was to regulate microglial activation by the combinatorial treatment of ciprofloxacin either with dexamethasone or celecoxib via targeting M1 and M2 polarization. The antibiotic-immunomodulator combinations were applied either by opening both TLR-2 and GR or neutralizing each of them. Our results confirmed that dexamethasone along with ciprofloxacin attenuated bacterial burden along with ROS production more efficiently than celecoxib combination during TLR-2 neutralization. FACS data indicated microglial M1 to M2 switching that was responsible for the better resolution of microglial inflammation.

Keywords: Celecoxib; Ciprofloxacin; Dexamethasone; Microglial inflammation; Polarization switching; S. aureus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Inflammatory Agents / administration & dosage
  • Cells, Cultured
  • Ciprofloxacin / administration & dosage*
  • Dexamethasone / administration & dosage*
  • Drug Therapy, Combination
  • Male
  • Mice
  • Microglia / drug effects
  • Microglia / metabolism*
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / metabolism*
  • Staphylococcus aureus*
  • Toll-Like Receptor 2 / antagonists & inhibitors
  • Toll-Like Receptor 2 / metabolism*

Substances

  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Ciprofloxacin
  • Dexamethasone