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Published on: July 19, 2018
Analysis of early mesothelial cell responses to Staphylococcus epidermidis isolated from patients with peritoneal
Amanda L McGuire1,2, Kieran T Mulroney1,2, Christine F Carson1,2
1Translational Renal Research Group, Harry Perkins Institute of Medical Research, Nedlands, Western Australia, Australia.
Abstract:
The major complication of peritoneal dialysis (PD) is the development of peritonitis, an infection within the abdominal cavity, primarily caused by bacteria. PD peritonitis is associated with significant morbidity, mortality and health care costs. Staphylococcus epidermidis is the most frequently isolated cause of PD-associated peritonitis. Mesothelial cells are integral to the host response to peritonitis, and subsequent clinical outcomes, yet the effects of infection on mesothelial cells are not well characterised. We systematically investigated the early mesothelial cell response to clinical and reference isolates of S. epidermidis using primary mesothelial cells and the mesothelial cell line Met-5A. Using an unbiased whole genome microarray, followed by a targeted panel of genes known to be involved in the human antibacterial response, we identified 38 differentially regulated genes (adj. p-value < 0.05) representing 35 canonical pathways after 1 hour exposure to S. epidermidis. The top 3 canonical pathways were TNFR2 signaling, IL-17A signaling, and TNFR1 signaling (adj. p-values of 0.0012, 0.0012 and 0.0019, respectively). Subsequent qPCR validation confirmed significant differences in gene expression in a number of genes not previously described in mesothelial cell responses to infection, with heterogeneity observed between clinical isolates of S. epidermidis, and between Met-5A and primary mesothelial cells. Heterogeneity between different S. epidermidis isolates suggests that specific virulence factors may play critical roles in influencing outcomes from peritonitis. This study provides new insights into early mesothelial cell responses to infection with S. epidermidis, and confirms the importance of validating findings in primary mesothelial cells.
Insights
Peritoneal dialysis (PD) peritonitis, often caused by Staphylococcus epidermidis, involves complex early responses from mesothelial cells. This study identified key signaling pathways and gene expression changes, highlighting isolate-specific variations in host response.
Area of Science:
- Microbiology
- Cell Biology
- Immunology
Background:
- Peritoneal dialysis (PD) peritonitis is a major complication, frequently caused by Staphylococcus epidermidis.
- Mesothelial cells play a crucial role in the host response to peritonitis, but their early responses to infection are not well understood.
Purpose of the Study:
- To systematically investigate the early mesothelial cell response to Staphylococcus epidermidis infection.
- To identify key molecular pathways and genes involved in the mesothelial cell reaction to S. epidermidis.
Main Methods:
- Primary mesothelial cells and the Met-5A cell line were exposed to clinical and reference isolates of S. epidermidis.
- Whole genome microarray and targeted gene expression analysis (qPCR) were employed to assess cellular responses.
- Differential gene expression and pathway analysis were performed after 1 hour of exposure.
Main Results:
- 38 differentially regulated genes and 35 canonical pathways were identified, with TNFR2, IL-17A, and TNFR1 signaling being prominent.
- Significant differences in gene expression were confirmed via qPCR, revealing novel mesothelial cell responses to infection.
- Heterogeneity in gene expression was observed between different S. epidermidis isolates and between primary cells and the Met-5A cell line.
Conclusions:
- This study provides novel insights into the early molecular responses of mesothelial cells to S. epidermidis infection.
- The observed heterogeneity suggests that specific bacterial virulence factors influence peritonitis outcomes.
- Validating findings in primary mesothelial cells is crucial for understanding PD-associated peritonitis.
