Murine myeloid‐derived suppressor cells are a source of elevated levels of interleukin‐27 in early life and compromise control of bacterial infection

Microbial infections early in life remain a major cause of infant mortality worldwide. This is consistent with immune deficiencies in this population. Interleukin (IL)‐27 is suppressive toward a variety of immune cell types, and we have shown that the production of IL‐27 is elevated in humans and mi...

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Published in:	Immunology and cell biology 2019-05, Vol.97 (5), p.445-456
Main Authors:	Gleave Parson, Madeline, Grimmett, Juanita, Vance, Jordan K, Witt, Michelle R, Seman, Brittany G, Rawson, Travis W, Lyda, Logan, Labuda, Christopher, Jung, Joo‐Yong, Bradford, Shelby D, Robinson, Cory M
Format:	Article
Language:	eng
Subjects:	Animals Animals, Newborn Bacteria Bacterial infections Cell activation Cytokines Escherichia coli - immunology Escherichia coli Infections - immunology Escherichia coli Infections - pathology Female Immune response Immune suppression Infant mortality infection Infections Interleukins - immunology interleukin‐27 Lymphocyte Activation Lymphocytes T Macrophages Macrophages - immunology Macrophages - pathology Male Meningitis Mice Myeloid-Derived Suppressor Cells - immunology Myeloid-Derived Suppressor Cells - pathology myeloid‐derived suppressor cells Neonates Sepsis Suppressor cells Surface markers T-Lymphocytes - immunology T-Lymphocytes - pathology
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Summary:	Microbial infections early in life remain a major cause of infant mortality worldwide. This is consistent with immune deficiencies in this population. Interleukin (IL)‐27 is suppressive toward a variety of immune cell types, and we have shown that the production of IL‐27 is elevated in humans and mice early in life. We hypothesize that elevated levels of IL‐27 oppose protective responses to infection during the neonatal period. In this study, we extended previous findings in neonatal mice to identify a population of IL‐27 producers that express Gr‐1 and were further identified as myeloid‐derived suppressor cells (MDSCs) based on the expression of surface markers and functional studies. In neonates, MDSCs are more abundant and contribute to the elevated pool of IL‐27 in this population. Although the ability of MDSCs to regulate T lymphocyte activation has been well‐studied, sparingly few studies have investigated the influence of MDSCs on innate immune function during bacterial infection. We demonstrate that macrophages are impaired in their ability to control growth of Escherichia coli when cocultured with MDSCs. This bacterium is a significant concern for neonates as a common cause of bacterial sepsis and meningitis. The suppressive effect of MDSCs on macrophage function is mediated by IL‐27; inclusion of a reagent to neutralize IL‐27 promotes improved control of bacterial growth. Taken together, these results suggest that the increased abundance of MDSCs may contribute to early life susceptibility to infection and further highlight production of IL‐27 as a novel MDSC mechanism to suppress immunity. IL‐27 levels are elevated in neonates. Myeloid‐derived suppressor cells (MDSCs) are more abundant in neonates and have been shown to be an important source of IL‐27. MDSCs oppose macrophage control of bacterial infection in an IL‐27‐dependent manner.
ISSN:	0818-9641 1440-1711