Human monocytes undergo functional re-programming during sepsis mediated by hypoxia-inducible factor-1α

Immunity
Irina N ShalovaSubhra K Biswas

Abstract

Sepsis is characterized by a dysregulated inflammatory response to infection. Despite studies in mice, the cellular and molecular basis of human sepsis remains unclear and effective therapies are lacking. Blood monocytes serve as the first line of host defense and are equipped to recognize and respond to infection by triggering an immune-inflammatory response. However, the response of these cells in human sepsis and their contribution to sepsis pathogenesis is poorly understood. To investigate this, we performed a transcriptomic, functional, and mechanistic analysis of blood monocytes from patients during sepsis and after recovery. Our results revealed the functional plasticity of monocytes during human sepsis, wherein they transited from a pro-inflammatory to an immunosuppressive phenotype, while enhancing protective functions like phagocytosis, anti-microbial activity, and tissue remodeling. Mechanistically, hypoxia inducible factor-1α (HIF1α) mediated this functional re-programming of monocytes, revealing a potential mechanism for their therapeutic targeting to regulate human sepsis.

References

Nov 1, 1991·The Journal of Clinical Investigation·C MunozJ M Cavaillon
Aug 2, 2002·Cell·Koichi KobayashiRichard A Flavell
Mar 12, 2003·Cell·Thorsten CramerRandall S Johnson
Apr 29, 2006·Current Opinion in Infectious Diseases·Eduardo López-CollazoCarlos del Fresno
Mar 29, 2008·American Journal of Respiratory and Critical Care Medicine·Sachin YendeUNKNOWN GenIMS Investigators
May 9, 2009·Nature Medicine·Richard S HotchkissThomas A Ferguson
May 19, 2009·Anesthesia and Analgesia·Christian TorgersenMartin W Dünser
Aug 26, 2009·Nature Reviews. Immunology·Victor Nizet, Randall S Johnson
Sep 29, 2009·Trends in Immunology·Subhra K Biswas, Eduardo Lopez-Collazo
Jun 29, 2010·European Journal of Immunology·Akihiro Kimura, Tadamitsu Kishimoto
Sep 30, 2010·The Journal of Experimental Medicine·Cesar A CorzoDmitry I Gabrilovich
Oct 28, 2010·JAMA : the Journal of the American Medical Association·Theodore J IwashynaKenneth M Langa
Dec 22, 2010·Expert Review of Anti-infective Therapy·Stephen W Standage, Hector R Wong
Dec 31, 2010·Critical Care : the Official Journal of the Critical Care Forum·Benjamin M TangAnthony S McLean
Mar 31, 2011·Blood·Johannes SchödelDavid R Mole
Jul 30, 2011·Critical Care : the Official Journal of the Critical Care Forum·Gordon P OttoNiels C Riedemann
Oct 15, 2011·Nature Reviews. Immunology·Peter J Murray, Thomas A Wynn
Nov 24, 2011·The Journal of Experimental Medicine·Wenzhong XiaoUNKNOWN Inflammation and Host Response to Injury Large-Scale Collaborative Research Program
Dec 22, 2011·JAMA : the Journal of the American Medical Association·Jonathan S BoomerRichard S Hotchkiss
Mar 28, 2012·Proceedings of the National Academy of Sciences of the United States of America·Kate SchroderMatthew J Sweet
Jul 10, 2012·Nature Medicine
Feb 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Junhee SeokUNKNOWN Inflammation and Host Response to Injury, Large Scale Collaborative Research Program
Nov 16, 2013·Nature Reviews. Immunology·Richard S HotchkissDidier Payen
Apr 22, 2014·Immunity·Clifford S Deutschman, Kevin J Tracey

❮ Previous
Next ❯

Citations

Feb 7, 2016·The Journal of Infection·Jesús F Bermejo-MartinEduardo Tamayo
Feb 6, 2016·Future Microbiology·Orhan Rasid, Jean-Marc Cavaillon
Mar 8, 2016·Nature Immunology·Shih-Chin ChengMihai G Netea
Nov 29, 2015·Medical Microbiology and Immunology·Sebastian F ZenkSteffen Stenger
Jul 21, 2015·Journal of Thrombosis and Haemostasis : JTH·J HawigerJ Zienkiewicz
Mar 19, 2015·Immunity·Derek W Gilroy, Simon Yona
Oct 12, 2015·Seminars in Immunology·Karim C El Kasmi, Kurt R Stenmark
Jul 29, 2015·Seminars in Immunology·Madhur P Motwani, Derek W Gilroy
Nov 13, 2015·Seminars in Immunology·Chiara PortaAntonio Sica
Dec 10, 2015·Stem Cells International·Louise A Mesentier-LouroMarcelo F Santiago
Feb 27, 2016·The Lancet. Respiratory Medicine·Emma E DavenportJulian C Knight
Jun 7, 2016·Seminars in Immunology·Melanie A Hamon, Jessica Quintin
May 18, 2016·Anesthesiology·Harmke D KiersMatthijs Kox
Jul 19, 2016·The Journal of Clinical Investigation·Gorjana RackovDimitrios Balomenos
Apr 25, 2017·Nature Reviews. Immunology·Tom van der PollMihai G Netea
Apr 5, 2018·Molecular and Cellular Pediatrics·Georg Varga, Dirk Foell
Mar 10, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Benjamin A FensterheimJulia K Bohannon
Jan 25, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Enrique Hernández-JiménezEduardo López-Collazo
Oct 31, 2017·Biomolecules & Therapeutics·Jinwook Shin, Mirim Jin
Mar 28, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Francesco BorrielloGianni Marone
Sep 17, 2016·Experimental Biology and Medicine·Javier Cabrera-PerezThomas S Griffith
Jul 18, 2018·QJM : Monthly Journal of the Association of Physicians·Y HuangX Su
Oct 22, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Rachel M KratofilJustin F Deniset
May 10, 2016·F1000Research·Darawan RinchaiDamien Chaussabel
Sep 23, 2018·The Journal of Biological Chemistry·Carlene PetesKatrina Gee
Nov 23, 2018·Bioscience Reports·Laurent M PaardekooperGeert van den Bogaart
Dec 24, 2018·Expert Review of Clinical Immunology·Niklas BruseMatthijs Kox
Feb 23, 2019·Viruses·Ashley A StegelmeierKhalil Karimi
Jun 18, 2017·The European Respiratory Journal·Enrique Hernández-JiménezEduardo López-Collazo
Oct 12, 2018·Biochemical Society Transactions·Abel AngMargreet C M Vissers
Nov 23, 2018·Inflammation·Dei-Fang ChenWen Meng
Dec 12, 2017·Nature Reviews. Nephrology·Fabienne Venet, Guillaume Monneret
Apr 16, 2019·The Pediatric Infectious Disease Journal·Jonathan P SturgeonAndrew J Prendergast
Sep 5, 2019·Journal of Clinical Medicine·Na-Ra HanHyun-Ja Jeong
Aug 22, 2017·Frontiers in Immunology·Katharina GiesbrechtDagmar Hildebrand

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.

Cancer -Omics

A variety of different high-throughput technologies can be used to identify the complete catalog of changes that characterize the molecular profile of cohorts of tumor samples. Discover the latest insights gained from cancer 'omics' in this feed.

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.

Bacterial Protein Structures

Bacterial protein structures can expedite the development of novel antibiotics. Here is the latest research on bacterial proteins and the resolution of their structures.

Related Papers

Nan fang yi ke da xue xue bao = Journal of Southern Medical University
Ya-li ZhangHong-min Zhu
World Journal of Stem Cells
Eleuterio LombardoWilfried Dalemans
European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies
S M PattonJ R Connor
© 2022 Meta ULC. All rights reserved