Myeloid-Derived Suppressor Cells Gain Suppressive Function during Neonatal Bacterial Sepsis

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.