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.
Highlights
It is important to characterize myeloid-derived suppressor cells (MDSCs) activity during an acute infection and the subsequent regulation of the immune response to deterduring an acute infection and the subsequent regulation of the immune response to determine if MDSCs may contribute to the susceptibility to an infection
We have shown that MDSCs are not static and change their functionality in response to E. coli O1:K1:H7, that MDSCs are not static and change their functionality in response to E. coli O1:K1:H7, an important serotype pathogenic to neonates
This suggested that MDSCs could be key regulators of the immune system during neonatal bacterial sepsis and other acute bacterial regulators of the immune system during neonatal bacterial sepsis and other acute bacterial infections
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. In 2018, UNICEF reported that 2.5 million infants did not survive the first 28 days of life, with a significant proportion of mortality related to infectious disease [1]. This vulnerability to an infection is consistent with a unique immune profile in neonates relative to adults. Disparities in cytokine production between adult and neonatal innate mononuclear cells have been reported following the bacterial ligand engagement of toll-like receptors (TLR) [2,3,4]. Previous studies have reported a decreased expression of
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