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Murine myeloid‐derived suppressor cells are a source of elevated levels of interleukin‐27 in early life and compromise control of bacterial infection
Author(s) -
Gleave Parson Madeline,
Grimmett Juanita,
Vance Jordan K,
Witt Michelle R,
Seman Brittany G,
Rawson Travis W,
Lyda Logan,
Labuda Christopher,
Jung JooYong,
Bradford Shelby D,
Robinson Cory M
Publication year - 2019
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.12224
Subject(s) - immune system , immunology , biology , population , myeloid derived suppressor cell , interleukin , cytokine , microbiology and biotechnology , suppressor , medicine , genetics , cancer , environmental health
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 ( MDSC s) based on the expression of surface markers and functional studies. In neonates, MDSC s are more abundant and contribute to the elevated pool of IL ‐27 in this population. Although the ability of MDSC s to regulate T lymphocyte activation has been well‐studied, sparingly few studies have investigated the influence of MDSC s 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 MDSC s. This bacterium is a significant concern for neonates as a common cause of bacterial sepsis and meningitis. The suppressive effect of MDSC s 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 MDSC s may contribute to early life susceptibility to infection and further highlight production of IL ‐27 as a novel MDSC mechanism to suppress immunity.