Long-term Monocyte Dysfunction after Sepsis in Humanized Mice Is Related to Persisted Activation of Macrophage-Colony Stimulation Factor (M-CSF) and Demethylation of PU.1, and It Can Be Reversed by Blocking M-CSF In Vitro or by Transplanting Naïve Autologous Stem Cells In Vivo

Frontiers in Immunology
Natalia LapkoKrzysztof Laudanski

Abstract

The duration of post-sepsis long-term immune suppression is poorly understood. Here, we focused on the role of monocytes (MO) as the pivotal cells for long-term regulation of post-sepsis milieu. Lost ability of MO to adapt is seen in several acute conditions, but it is unclear for how long MO aberrancy post-sepsis can persist. Interestingly, the positive feedback loop sustaining secretion of macrophage-colony stimulation factor (M-CSF) can persist even after resolution of sepsis and significantly alters performance of MO. Here, we investigated the activation of M-CSF, and it as critical regulator of PU.1 in mice surviving 28 days after sepsis. Our primary readout was the ability of MO to differentiate into dendritic cells (DCs; MO→iDC) in vitro since this is one of the critical processes regulating a successful transition from innate to acquired immunity. We utilized a survival modification of the cecal ligation and puncture (CLP) model of sepsis in humanized mice. Animals were sacrificed 28 days after CLP (tCLP+28d). Untouched (CONTR) or sham-operated (SHAM) animals served as controls. Some animals received rescue from stem cells originally used for grafting 2 weeks after CLP. We found profound decrease of MO→iDC in the humani...Continue Reading

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Citations

Oct 2, 2020·Scientific Reports·Chloé Albert VegaSophie Trouillet-Assant
Jul 7, 2018·Frontiers in Immunology·Benjamin G Chousterman, Marine Arnaud
Jun 24, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sara E HamiltonThomas S Griffith
Jan 16, 2021·Trends in Immunology·Amy RobinsonJeffrey W Pollard
Mar 7, 2021·International Journal of Molecular Sciences·Krzysztof Laudanski
Jun 3, 2021·International Journal of Molecular Sciences·Krzysztof LaudanskiKathleen E Sullivan
Dec 7, 2021·Frontiers in Cardiovascular Medicine·Nicholas FeliciKrzysztof Laudanski

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Methods Mentioned

BETA
flow cytometry
FACS
PCR
transfection

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CpG Island Finder
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