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Updated: Oct 30, 2025
A Neonatal Imaging Model of Gram-Negative Bacterial Sepsis
Published on: August 12, 2020
Myeloid-Derived Suppressor Cells Gain Suppressive Function during Neonatal Bacterial Sepsis
Jordan K Vance1, Travis W Rawson1, Jessica M Povroznik1
1Department of Microbiology, Immunology, and Cell Biology, West Virginia University School of Medicine, Morgantown, WV 26506, USA.
Insights
Neonates have more myeloid-derived suppressor cells (MDSCs) which increase immune suppression during bacterial sepsis. These cells, activated by bacterial components, hinder protective T cell responses in early life infections.
Area of Science:
- Immunology
- Neonatal Research
- Microbiology
Background:
- Neonates exhibit heightened susceptibility to infections.
- Increased abundance of myeloid-derived suppressor cells (MDSCs) in neonates compared to older individuals contributes to immune vulnerability.
Purpose of the Study:
- To investigate the immunomodulatory role of MDSCs in neonatal bacterial sepsis.
- To understand how MDSCs' immune suppressive functions are altered during infection in neonates.
Main Methods:
- Utilized a murine model of neonatal bacterial sepsis.
- Conducted gene expression analysis of MDSCs in response to *Escherichia coli* O1:K1:H7.
- Assessed MDSC responses to specific pathogen-associated molecular patterns (PAMPs) like LPS, peptidoglycan, and flagellin.
- Measured the impact of MDSCs on CD4+ T cell proliferation.
Main Results:
- Neonatal MDSCs upregulate NOS2, Arg-1, and IL-27p28 expression in response to *E. coli*, enhancing immune suppressive functions.
- MDSC activation is regulated at the gene expression level, leading to increased enzymatic activity and cytokine secretion.
- Neonatal MDSCs express TLRs 2, 4, and 5, recognizing bacterial PAMPs, but responses to individual PAMPs vary.
- Upregulation of NOS2 occurred with LPS, peptidoglycan, and flagellin, while Arg-1 and IL-27p28 responses were less consistent with individual PAMPs.
- Enhanced MDSC immune suppression led to reduced CD4+ T cell proliferation.
Conclusions:
- Neonatal MDSCs dynamically modulate their activity during bacterial infections.
- These cells can acquire potent immune suppressive capabilities in early life, potentially impairing protective immunity against infections.
Abstract:
Neonates are at an increased risk of an infectious disease. This is consistent with an increased abundance of myeloid-derived suppressor cells (MDSCs) compared with older children and adults. Using a murine model of neonatal bacterial sepsis, we demonstrate that MDSCs modulate their activity during an infection to enhance immune suppressive functions. A gene expression analysis shows that MDSCs increased NOS2, Arg-1 and IL-27p28 expression in vitro and in vivo in response to Escherichia coli O1:K1:H7 and this is regulated at the level of the gene expression. Changes in the effector gene expression are consistent with increased enzymatic activity and cytokine secretion. The neonatal MDSCs express toll-like receptor (TLR) 2, 4 and 5 capable of recognizing pathogen-associated molecular patterns (PAMPS) on E. coli. However, a variable level of effector expression was achieved in response to LPS, peptidoglycan or flagellin. Individual bacterial PAMPs did not stimulate the expression of Arg-l and IL-27p28 equivalently to E. coli. However, the upregulation of NOS2 was achieved in response to LPS, peptidoglycan and flagella. The increased immune suppressive profile translated to an enhanced suppression of CD4+ T cell proliferation. Collectively, these findings increase our understanding of the dynamic nature of MDSC activity and suggest that these cells abundant in early life can acquire activity during an infection that suppresses protective immunity.
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