Format

Send to

Choose Destination
See comment in PubMed Commons below
Immunity. 2015 Mar 17;42(3):484-98. doi: 10.1016/j.immuni.2015.02.001. Epub 2015 Mar 3.

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

Author information

  • 1Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Biopolis, #04-06 Immunos building, 8A Biomedical Grove, Singapore 138648, Singapore.
  • 2Department of Pediatrics and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
  • 3Tumor Immunology Lab and Innate Immunity Group, IdiPAZ, "La Paz" Hospital, Pseo de La Castellana 261, Madrid 28046, Spain.
  • 4Development Therapeutic Program, Tumor Hypoxia Laboratory, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, Frederick, MD 21701, USA.
  • 5Department of Internal Medicine, "La Paz" Hospital, Pseo de La Castellana 261, Madrid 28046, Spain.
  • 6Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Biopolis, #04-06 Immunos building, 8A Biomedical Grove, Singapore 138648, Singapore. Electronic address: subhra_biswas@immunol.a-star.edu.sg.

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.

PMID:
25746953
DOI:
10.1016/j.immuni.2015.02.001
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center