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 L Kielian

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9 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
Publication statusPublished - Jul 1 2018

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Keywords

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

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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