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

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

Highlights

• Our study shows for the first time a differential inflammatory response evoked by MRSA vs MSSA in microglia and RPE cells in orchestrating retinal innate response in endophthalmitis.

• Higher expression of IL-1β, IL-8, 1L-10, IL-6, and GM-CSF was observed in MRSA-infected cells compared to MSSA-challenged cells.

• We speculate that multidrug phenotype of infecting pathogen should be considered not only to choose appropriate antibiotic but also warrants objective examinations of immune system and use of anti-inflammatory therapeutic modulators for a more tangible approach.

Acknowledgments

Hyderabad Eye Research Foundation for funding support. The authors also thank Dr. Inderjeet Kaur for providing the Retinal Pigment cells (ARPE-19) and human microglial cell line (CHME3) as well as Dr. Vivek Singh (CORE, L V Prasad Eye Institute, Hyderabad, India) for helping with validation experiments using immunofluorescence assay.

Author contributions

P.N.- acquisition of data, and analysis of data, drafting the article; J.J.- conception and design of the study, interpretation of data, revising it critically for intellectual content and final approval of the version to be submitted.

Conflicts of interest

The authors declare no conflict of interest.

Additional information

Funding

This research was funded by DST-SERB to Dr Joveeta Joseph (File Number: CRG/2019/004386) India.