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Updated: Jul 4, 2026
A Retrograde Implantation Approach for Peritoneal Dialysis Catheter Placement in Mice
Published on: July 20, 2022
Receptor-interacting protein-2 deficiency delays macrophage migration and increases intracellular infection during
Michelle L McCully1, Todd Fairhead, Chantal S Colmont
1FOCIS Centre for Clinical Immunology and Immunotherapeutics, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
Background:
Early upregulation of receptor-interacting protein-2 (RIP2) expression during peritoneal dialysis (PD)-associated peritonitis correlates with a favorable clinical outcome, while failure to upregulate RIP2 correlates with a protracted course. We noticed that patients who do not upregulate RIP2 during PD-associated peritonitis have more peritoneal macrophages during the early phase of infection.
Methods:
To study the mechanism behind this observation, we examined the role of RIP2 in the immune response to bacterial challenge in a mouse model of acute peritonitis. We injected RIP2(+/+) and RIP2(-/-) mice intraperitoneally with a Staphylococcus epidermidis cell free-preparation, and peritoneal cells were isolated 3, 6 and 24 h after challenge.
Results:
Surprisingly, RIP2(-/-) mice had a comparable influx of inflammatory leukocytes, but had a significantly higher number of peritoneal macrophages at 3 h, indicating delayed emigration of these cells. No significant differences were seen at later times suggesting that migration was delayed but not inhibited. In addition, RIP2(-/-) macrophages were more permissive to intracellular infection by Staphylococcus aureus, indicating that, in the absence of RIP2, resident peritoneal macrophages could become reservoirs of bacteria.
Conclusion:
These findings provide a mechanism for the observation that upregulation of RIP2 expression is required for rapid resolution of peritonitis, by decreasing intracellular infection and by regulating the migration of antigen-presenting cells in the early stages of an inflammatory response.
Insights
Receptor-interacting protein-2 (RIP2) is crucial for resolving peritonitis. Its absence delays macrophage migration and allows bacteria to persist in macrophages, hindering recovery from infection.
Area of Science:
- Immunology
- Cell Biology
- Peritoneal Dialysis Research
Background:
- Receptor-interacting protein-2 (RIP2) upregulation correlates with better outcomes in peritoneal dialysis (PD)-associated peritonitis.
- Failure to upregulate RIP2 is linked to prolonged peritonitis and increased early peritoneal macrophages.
Purpose of the Study:
- To investigate the role of RIP2 in the immune response during acute peritonitis.
- To elucidate the mechanism behind increased peritoneal macrophages in patients with low RIP2 expression.
Main Methods:
- Utilized a mouse model of acute peritonitis induced by Staphylococcus epidermidis.
- Compared immune cell responses, specifically peritoneal macrophages and leukocytes, in RIP2(+/+) and RIP2(-/-) mice at 3, 6, and 24 hours post-challenge.
- Assessed macrophage permissiveness to intracellular Staphylococcus aureus infection.
Main Results:
- RIP2(-/-) mice exhibited delayed peritoneal macrophage emigration but comparable leukocyte influx.
- Resident peritoneal macrophages in RIP2(-/-) mice were more susceptible to intracellular Staphylococcus aureus infection.
- These findings suggest RIP2 is essential for rapid resolution by controlling macrophage migration and intracellular bacterial load.
Conclusions:
- RIP2 upregulation is necessary for the rapid resolution of peritonitis.
- RIP2 regulates early inflammatory responses, including antigen-presenting cell migration.
- RIP2 plays a key role in preventing intracellular bacterial reservoirs within macrophages.
