β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance
Cell. 2016-11-17;167(5):1354-1368.e14.
- Abstract
- Innate immune memory is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components such as lipopolysaccharide (LPS). We apply an integrated epigenomic approach to characterize the molecular events involved in LPS-induced tolerance in a time-dependent manner. Mechanistically, LPS-treated monocytes fail to accumulate active histone marks at promoter and enhancers of genes in the lipid metabolism and phagocytic pathways. Transcriptional inactivity in response to a second LPS exposure in tolerized macrophages is accompanied by failure to deposit active histone marks at promoters of tolerized genes. In contrast, β-glucan partially reverses the LPS-induced tolerance in vitro. Importantly, ex vivo β-glucan treatment of monocytes from volunteers with experimental endotoxemia re-instates their capacity for cytokine production. Tolerance is reversed at the level of distal element histone modification and transcriptional reactivation of otherwise unresponsive genes. VIDEO ABSTRACT.
- Consortium data used in this publication
- Raw data files for RNA sequencing This paper GEO: GSE85243 Raw data files for ChIP sequencing This paper GEO: GSE85245 Raw data files for ATAC sequencing This paper GEO: GSE87218 Raw data files for WGBS sequencing This paper EGA: EGAD00001002693
- Datasets
- DSR970XLO, DSR261HEQ, DSR626XPQ, DSR294TQM, DSR570QMF, DSR235FBB, DSR027MJY, DSR412HGU, DSR439QVH, DSR119GEO, DSR516MVY, DSR282UKE, DSR400QXY, DSR831GAV, DSR402OWE, DSR920OPS, DSR245WKV, DSR017REG, DSR104YYJ, DSR432IFA, DSR109EEK, DSR977WLQ, DSR397QCJ, DSR840QWJ, DSR826ZWP, DSR738OTN, DSR573CYC, DSR329ZII, DSR067KMF, DSR403KXI, DSR189NFY, DSR082KYM, DSR911UHJ, DSR108AZI, DSR016AJU, DSR781BAK, DSR860BBA, DSR356LED, DSR849WXC, DSR987DNE, DSR052GHS, DSR668PAN, DSR526KYA, DSR890NNI, DSR552EKW, DSR122CAJ, DSR909LYK, DSR851UZK, DSR777PED, DSR109ZXS, DSR455FHD, DSR062UBG, DSR070MUR, DSR767GNC, DSR704SCW, DSR217VBP, DSR793NBU, DSR471OUM, DSR903EQN, DSR358LMN, DSR654PMK, DSR382JSZ, DSR679XJR, DSR804JWH, DSR324UZU, DSR050XFQ, DSR297YTV, DSR010VSN, DSR160ZNS, DSR303WJG, DSR672IHC, DSR171SJU, DSR837PMC, DSR696DSB, DSR870QZR, DSR319IWK, DSR787ZVE, DSR074TRX, DSR789JAJ, DSR907EGY, DSR602CYK, DSR818FOJ, DSR040ZJJ, DSR859JQG, DSR871XCG, DSR833JIH, DSR186TDJ, DSR091JLV, DSR289VNA, DSR036RBB, DSR107AXO, DSR871PCP, DSR283IBC, DSR978KHJ, DSR197NWS, DSR978YES, DSR228VFG, DSR175OTX, DSR084XEY, DSR016TVA, DSR601REX, DSR080UMT, DSR438HAQ, DSR169TJA, DSR773FOT, DSR342UXO, DSR111VUO, DSR412YPY, DSR140ISE, DSR401DQT, DSR974CEF, DSR800ZKK, DSR935QGD, DSR080DNH, DSR261KXA, DSR229PCE, DSR796EAR, DSR650GPE, DSR877BRW, DSR821XCG, DSR541TCU, DSR112GDK, DSR577JTH, DSR546LIB, DSR397YCO, DSR258EDL, DSR999BSV, DSR026EDM, DSR245GGA, DSR468ZSR, DSR884JBU, DSR324LLG, DSR448SRG, DSR177BAQ, DSR348WZF, DSR582ZNR, DSR982TIR, DSR005KHX, DSR593NPV, DSR524WZB, DSR227LKV, DSR831PYL, DSR992NHC, DSR983LGA, DSR031EDT, DSR937QPF, DSR773CXD, DSR573VIF, DSR468OET, DSR324RXQ, DSR281QKE, DSR098PFJ, DSR857GDR, DSR030FPP, DSR244HDC, DSR110TAE, DSR383LEV, DSR716ZZT, DSR528PHX, DSR230NRH, DSR397ONR, DSR934UQW, DSR697HCX, DSR398SSK, DSR481SFJ, DSR121PJD, DSR046NHR, DSR659GJL, DSR855BYB, DSR186OAN, DSR742HYH, DSR713MBG, DSR249ZXB, DSR044QHH, DSR690ZQS, DSR874VEO, DSR387CHY, DSR861NMR, DSR908PCK, DSR894ESI, DSR040UNQ, DSR000FLL, DSR669BSO, DSR138VHU, DSR034ZNQ, DSR106KTE, DSR412GWK, DSR710EBY, DSR123SDA, DSR873SZS, DSR698TJB, DSR220BWN, DSR424JZN, DSR775NYE, DSR122IWH, DSR513ZPW, DSR588JIC, DSR772ERF, DSR324XXB, DSR126ZHG, DSR751JQK, DSR945INA, DSR252EWN, DSR541NWK, DSR594CIB, DSR806FTS, DSR877GMC, DSR277QAP, DSR358JPO, DSR451XYK, DSR331VTS, DSR571OEB, DSR843ENW, DSR778HGA, DSR136YMF, DSR049PCN, DSR634ADB, DSR920FDN, DSR875GGI, DSR642AXP, DSR472AWT, DSR110DSK, DSR260TIJ, DSR135OVL, DSR259WDX, DSR503VVK, DSR825AMW, DSR477MOZ, DSR298NAN, DSR856YOV, DSR901KOQ, DSR065OEH, DSR468YVV, DSR205EVJ, DSR660FOW, DSR215ALV, DSR751TNS, DSR102LRA, DSR968UJL, DSR359YWY, DSR703ZXV, DSR019CTT, DSR573QGD