Single cell ATAC sequencing identifies sleepy macrophages during reciprocity of cytokines in L.major infection

Abstract

Hallmark for macrophages is their ability to possess plasticity which enables them to respond to changing microenvironment. Leishmania takes 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 for L.major infection 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. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/526191v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@f655c7org.highwire.dtl.DTLVardef@79b2adorg.highwire.dtl.DTLVardef@1c1a628org.highwire.dtl.DTLVardef@83a6a3_HPS_FORMAT_FIGEXP M_FIG Graphical abstract summary of single cell ATAC sequencing for L.major infected 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. C_FIG