PT  - JOURNAL ARTICLE
AU  - Tara E. Sutherland
AU  - Tovah N. Shaw
AU  - Rachel Lennon
AU  - Sarah E. Herrick
AU  - Dominik Rückerl
TI  - Ongoing exposure to peritoneal dialysis fluid alters resident peritoneal macrophage phenotype and activation propensity
AID  - 10.1101/2020.03.02.973404
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.03.02.973404
4099  - http://biorxiv.org/content/early/2020/03/18/2020.03.02.973404.short
4100  - http://biorxiv.org/content/early/2020/03/18/2020.03.02.973404.full
AB  - Peritoneal dialysis (PD) is a more continuous alternative to haemodialysis, for patients with chronic kidney disease, with considerable initial benefits for survival, patient independence and healthcare cost. However, longterm PD is associated with significant pathology, negating the positive effects over haemodialysis. Importantly, peritonitis and activation of macrophages is closely associated with disease progression and treatment failure. However, recent advances in macrophage biology suggest opposite functions for macrophages of different cellular origins. While monocyte-derived macrophages promote disease progression in some models of fibrosis, tissue resident macrophages have rather been associated with protective roles. Thus, we aimed to identify the relative contribution of tissue resident macrophages to PD induced inflammation in mice. Unexpectedly, we found an incremental loss of homeostatic characteristics, anti-inflammatory and efferocytic functionality in peritoneal resident macrophages, accompanied by enhanced inflammatory responses to external stimuli. Thus, alterations in tissue resident macrophages may render longterm PD patients sensitive to developing peritonitis and consequently fibrosis/sclerosis.