Abstract

The inflammatory activation and recruitment of defined myeloid populations is essential for controlling the bridge between innate and adaptive immunity and shaping the immune response to microbial challenge. However, these cells exhibit significant functional heterogeneity and the inflammatory signals that differentially influence their effector characteristics are poorly characterized. In this study, we defined the phenotype of discrete subsets of effective antigen‐presenting cells (APCs) in the peritoneal cavity during peritonitis. When the functional properties of these cells were compared to inflammatory monocyte‐derived macrophages we noted differential responses to the immune‐modulatory cytokine IL‐10. In contrast to the suppressive actions of IL‐10 on inflammatory macrophages, the recruitment of APCs was relatively refractory and we found no evidence for selective inhibition of APC differentiation. This differential response of myeloid cell subsets to IL‐10 may thus have limited impact on development of potentially tissue‐damaging adaptive immune responses, while restricting the magnitude of the inflammatory response. These findings may have clinical relevance in the context of peritoneal dialysis patients, where recurrent infections are associated with immune‐mediated membrane dysfunction, treatment failure, and increased morbidity.

Highlights

  • Local immunity in the peritoneal cavity contributes to the failure of peritoneal dialysis (PD) as a treatment for end-stage kidney disease

  • Identification of peritoneal antigen presenting cell · dendritic cells (DC) (APC) subsets tion, published microarray data that compared peritoneal ‘F4/80lowMHCII+’ with ‘F4/80intMHCII+’ InfMØ during thioglycollate-induced peritonitis were analyzed for differences (Supporting Information Table 1) [17]

  • We recently demonstrated the role of a specific adaptive immune response in the development of fibrotic tissue damage following recurrent peritonitis [5]

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Summary

Introduction

Local immunity in the peritoneal cavity contributes to the failure of peritoneal dialysis (PD) as a treatment for end-stage kidney disease. In this context, peritoneal infection is a major driver,. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Positive outcome of infectious peritonitis in PD patients is associated with Th1-like responses [4] and we recently demonstrated a role for IL-6/IFNγ/STAT1dependent adaptive immunity in the development of fibrotic tissue damage following recurrent peritonitis [5]. Limited information is currently available on the innate sensing cells that control these downstream adaptive immune responses and control of local immune responses could feasibly alleviate tissue damage

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