Difference in Host Immune response to Methicillin-Resistant and Methicillin Sensitive Staphylococcus aureus (MRSA and MSSA) Endophthalmitis

Ocul Immunol Inflamm. 2022 Jul;30(5):1044-1054. doi: 10.1080/09273948.2020.1859551. Epub 2021 Feb 9.

Abstract

Purpose: The study aimed to understand the differential immune response of methicillin susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains in in vitro models of endophthalmitis.

Methods: Retinal pigment epithelium (RPE) and microglia cells (CHME-3) were exposed to MRSA and MSSA strains and analyzed for expression of inflammatory mediators by real-time quantitative PCR and validated by ELISA or immunofluorescence assay. Heatmap and STRING analysis was used to assess the differential immune expression.

Results: Both microglia and RPE expressed TLR-2, TLR-1, TLR-6, and TLR -9 after challenge with MRSA and MSSA strains though the expression varied. MRSA-infected cells induced higher expression of IL-1β, IL-8, 1 L-10, IL-6, and GM-CSF, while TNF-α and IFN-ϒ were downregulated in comparison to MSSA-infected cells. We also demonstrate that MRSA infection leads to increased activation of MMP-9 and MMP-2 in RPE cells, while microglia expressed only MMP-9 in MRSA-infected cells.

Conclusions: MRSA strain can induce an exacerbated immune response in retinal cells. Giving clues for potential targets in immunomodulatory therapies.

Keywords: Microglia; RPE; S. aureus; endophthalmitis; innate immune response.

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Endophthalmitis* / drug therapy
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Humans
  • Immunity
  • Interleukin-6
  • Interleukin-8
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9 / genetics
  • Methicillin / pharmacology
  • Methicillin Resistance
  • Methicillin-Resistant Staphylococcus aureus*
  • Microbial Sensitivity Tests
  • Staphylococcal Infections* / drug therapy
  • Staphylococcus aureus
  • Toll-Like Receptor 1
  • Toll-Like Receptor 2
  • Toll-Like Receptor 6
  • Tumor Necrosis Factor-alpha

Substances

  • Anti-Bacterial Agents
  • Interleukin-6
  • Interleukin-8
  • Toll-Like Receptor 1
  • Toll-Like Receptor 2
  • Toll-Like Receptor 6
  • Tumor Necrosis Factor-alpha
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Methicillin