Single cell ATAC sequencing identifies sleepy macrophages during reciprocity of cytokines inL.majorinfection

Abstract

AbstractHallmark for macrophages is their ability to possess plasticity which enables them to respond to changing microenvironment.Leishmaniatakes use of the phenotypic plasticity of macrophages to create favorable position for intracellular survival and persistent infection through regulatory cytokine like IL10. However, these effector cells can eliminate infection through modulation of critical cytokines such as IL12 and key players involved in its production. Using sophisticated tool of single cell ATAC sequencing we analyzed the regulatory axis of IL10 and IL12 in time dependent manner forL.majorinfection in macrophages. We recognized the cellular heterogeneity post infection with the regulators of IL10 and IL12 and observed a reciprocal relationship between them. Our prominent findings also exposed sleepy macrophages and its role in IL10 and IL12 reciprocity. To summarize, role of NFAT5 was vital in identification of sleepy macrophages which is a transient state where transcription factors controlled the epigenetic remodeling and expression of genes involved in pro-inflammatory cytokine production and recruitment of immune cells.Abstract FigureGraphical abstract summary of single cell ATAC sequencing forL.majorinfected RAW264.7 mouse macrophage cell line. (A) Reciprocal relationship identified in cell populations which is governed through chromatin remodeling. (B) Single cell ATAC pipeline for analysis of dataset (C) Identification of sleepy macrophages which may play potential role in reciprocity.