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Accession IconSRP124807

Western diet triggers NLRP3-dependent persistent functional reprogramming of myeloid cells II [RNA-Seq]

Organism Icon Mus musculus
Sample Icon 19 Downloadable Samples
Technology Badge IconIllumina HiSeq 1500

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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 undectable in serum soon after mice were shifted back to chow diet (CD). In contrast, myeloid cell responses towards innate stimuli remained broadly augmented. WD induced transcriptomic and epigenomic reprogramming of myeloid progenitor cells, leading to increased proliferation as well as enhanced innate immune and interferon responses towards in vivo LPS challenge. QTL analysis in human monocytes trained with oxidized low-density lipoprotein (oxLDL) and stimulated with LPS suggested inflammasome-mediated trained immunity. Consistently, Nlrp3-/-/Ldlr-/--deficient mice lacked WD-induced systemic inflammation or myeloid progenitor proliferation and reprogramming. Hence, NLRP3 mediates trained immunity following WD and could thereby arbitrate the potentially deleterious effects of trained immunity in inflammatory diseases. Overall design: Examination of GMPs in six different conditions by RNA-seq
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