Arginase-1 expression in myeloid cells regulates Staphylococcus aureus planktonic but not biofilm infection

Kelsey J. Yamada, Cortney E. Heim, Amy L. Aldrich, Casey M. Gries, Anna G. Staudacher, Tammy Kielian

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Staphylococcus aureus is a leading cause of device-associated biofilm infections, which represent a serious health care concern based on their chronicity and antibiotic resistance. We previously reported that S. aureus biofilms preferentially recruit myeloid-derived suppressor cells (MDSCs), which promote monocyte and macrophage anti-inflammatory properties. This is associated with increased myeloid arginase-1 (Arg-1) expression, which has been linked to anti-inflammatory and profibrotic activities that are observed during S. aureus biofilm infections. To determine whether MDSCs and macrophages utilize Arg-1 to promote biofilm infection, Arg-1 was deleted in myeloid cells by use of Tie-2Cre mice. Despite Arg-1 expression in biofilm-associated myeloid cells, bacterial burdens and leukocyte infiltrates were similar between wild-type (WT) and Arg-1fl/fl;Tie-2Cre conditional knockout (KO) mice from days 3 to 14 postinfection in both orthopedic implant and catheter-associated biofilm models. However, inducible nitric oxide synthase (iNOS) expression was dramatically elevated in biofilm-associated MDSCs from Arg-1fl/fl;Tie-2Cre animals, suggesting a potential Arg-1-independent compensatory mechanism for MDSCmediated immunomodulation. Treatment of Arg-1fl/fl;Tie-2Cre mice with the iNOS inhibitor N6-(1-iminoethyl)-L-lysine (L-NIL) had no effect on biofilm burdens or immune infiltrates, whereas treatment of WT mice with the Arg-1/ornithine decarboxylase inhibitor difluoromethylornithine (DFMO) increased bacterial titers, but only in the surrounding soft tissues, which possess attributes of a planktonic environment. A role for myeloid-derived Arg-1 in regulating planktonic infection was confirmed using a subcutaneous abscess model, in which S. aureus burdens were significantly increased in Arg-1fl/fl;Tie-2Cre mice compared to those in WT mice. Collectively, these results indicate that the effects of myeloid Arg-1 are context dependent and are manifest during planktonic but not biofilm infection.

Original languageEnglish (US)
Article numbere00206-18
JournalInfection and immunity
Volume86
Issue number7
DOIs
StatePublished - Jul 1 2018

Keywords

  • Arginase-1
  • Biofilm
  • Macrophage
  • Myeloid-derived suppressor cell
  • S. aureus

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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