CD206 expression characterizes an inflammatory, resident human peritoneal macrophage subset in decompensated cirrhosis

Question:

Peritoneal macrophages (PM) regulate inflammation and control bacterial infections in decompensated cirrhosis. The aim of this study was to characterize human PM heterogeneity and link PM activation with the outcome of spontaneous bacterial peritonitis (SBP).

Methods:

We phenotypically and functionally characterized human PM by flow cytometry, transcriptome-wide analysis of differential gene expression, ex vivo stimulation, and quantifying the soluble form of the mannose receptor CD206 in a cohort of patients with decompensated cirrhosis in absence and presence of SBP.

Results:

Employing CD206 surface expression, we identified subsets of human large (LPM) and small PM (SPM), which differed in granularity and maturation. PM subsets from patients with decompensated cirrhosis revealed discrete transcriptome clusters, comprising more than 4,000 differentially regulated genes involved in cell cycle, metabolism, self-renewal, and immune signaling. In contrast to SPM, LPM displayed a resident inflammatory phenotype, released higher levels of TNF after stimulation, and were less susceptible to tolerance induction. CD206 expression and release from LPM could be manipulated by incubating PM with TLR2/TLR6 and TLR4 agonists in vitro. Serial clinical samples revealed a relative depletion of LPM in the early phase of SBP followed by a recovery after treatment. Higher AF concentrations of sCD206 identified patients with SBP and indicated poor survival after 90 days.

Conclusions:

CD206 expression indicates a subset of mature, resident, inflammatory human PM. AF concentrations of its soluble form predict outcome of SBP.