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Epigenomic and transcriptomic analyses reveal differences between low-grade inflammation and severe exhaustion in LPS-challenged murine monocytes.
Naler, Lynette B; Hsieh, Yuan-Pang; Geng, Shuo; Zhou, Zirui; Li, Liwu; Lu, Chang.
  • Naler LB; Department of Chemical Engineering, Virginia Tech, Blacksburg, VA, USA.
  • Hsieh YP; Department of Chemical Engineering, Virginia Tech, Blacksburg, VA, USA.
  • Geng S; Department of Biological Sciences, Virginia Tech, Blacksburg, VA, USA.
  • Zhou Z; Department of Chemical Engineering, Virginia Tech, Blacksburg, VA, USA.
  • Li L; Department of Biological Sciences, Virginia Tech, Blacksburg, VA, USA. lwli@vt.edu.
  • Lu C; Department of Chemical Engineering, Virginia Tech, Blacksburg, VA, USA. changlu@vt.edu.
Commun Biol ; 5(1): 102, 2022 01 28.
Article in English | MEDLINE | ID: covidwho-1655635
ABSTRACT
Emerging studies suggest that monocytes can be trained by bacterial endotoxin to adopt distinct memory states ranging from low-grade inflammation to immune exhaustion. While low-grade inflammation may contribute to the pathogenesis of chronic diseases, exhausted monocytes with pathogenic and immune-suppressive characteristics may underlie the pathogenesis of polymicrobial sepsis including COVID-19. However, detailed processes by which the dynamic adaption of monocytes occur remain poorly understood. Here we exposed murine bone-marrow derived monocytes to chronic lipopolysaccharide (LPS) stimulation at low-dose or high-dose, as well as a PBS control. The cells were profiled for genome-wide H3K27ac modification and gene expression. The gene expression of TRAM-deficient and IRAK-M-deficient monocytes with LPS exposure was also analyzed. We discover that low-grade inflammation preferentially utilizes the TRAM-dependent pathway of TLR4 signaling, and induces the expression of interferon response genes. In contrast, high dose LPS uniquely upregulates exhaustion signatures with metabolic and proliferative pathways. The extensive differences in the epigenomic landscape between low-dose and high-dose conditions suggest the importance of epigenetic regulations in driving differential responses. Our data provide potential targets for future mechanistic or therapeutic studies.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Monocytes / Lipopolysaccharides / Epigenomics / Transcriptome / Inflammation Limits: Animals Language: English Journal: Commun Biol Year: 2022 Document Type: Article Affiliation country: S42003-022-03035-2

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Monocytes / Lipopolysaccharides / Epigenomics / Transcriptome / Inflammation Limits: Animals Language: English Journal: Commun Biol Year: 2022 Document Type: Article Affiliation country: S42003-022-03035-2