Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2018 Jan 13

PMID 29328911

Citations 480

Authors

Anette Christ

Patrick Gunther

Mario A R Lauterbach

Peter Duewell

Debjani Biswas

Karin Pelka

Claus J Scholz

Marije Oosting

Kristian Haendler

Kevin Bassler

Kathrin Klee

Jonas Schulte-Schrepping

Thomas Ulas

Simone J C F M Moorlag

Vinod Kumar

Min Hi Park

Leo A B Joosten

Laszlo A Groh

Niels P Riksen

Terje Espevik

Andreas Schlitzer

Yang Li

Michael L Fitzgerald

Mihai G Netea

Joachim L Schultze

Eicke Latz

Affiliations

Soon will be listed here.

Abstract

Long-term epigenetic reprogramming of innate immune cells in response to microbes, also termed "trained immunity," causes prolonged altered cellular functionality to protect from secondary infections. Here, we investigated whether sterile triggers of inflammation induce trained immunity and thereby influence innate immune responses. Western diet (WD) feeding of Ldlr mice induced systemic inflammation, which was undetectable in serum soon after mice were shifted back to a chow diet (CD). In contrast, myeloid cell responses toward innate stimuli remained broadly augmented. WD-induced transcriptomic and epigenomic reprogramming of myeloid progenitor cells led to increased proliferation and enhanced innate immune responses. Quantitative trait locus (QTL) analysis in human monocytes trained with oxidized low-density lipoprotein (oxLDL) and stimulated with lipopolysaccharide (LPS) suggested inflammasome-mediated trained immunity. Consistently, Nlrp3/Ldlr mice lacked WD-induced systemic inflammation, myeloid progenitor proliferation, and reprogramming. Hence, NLRP3 mediates trained immunity following WD and could thereby mediate the potentially deleterious effects of trained immunity in inflammatory diseases.

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