Orosomucoid 1 drives opportunistic infections through the polarization of monocytes to the M2b phenotype

Kiwamu Nakamura, Ichiaki Ito, Makiko Kobayashi, David N. Herndon, Fujio Suzuki

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Orosomucoid (ORM, composed of two isoforms, ORM1 and ORM2) has been described as an inducer of M2 macrophages, which are cells that decrease host antibacterial innate immunities. However, it is unknown which phenotypes of M2 macrophages are induced by ORM. In this study, healthy donor monocytes stimulated with ORM (ORM-monocytes) were characterized phenotypically and biologically. CCL1 (a biomarker of M2b macrophages) and IL-10 were detected in monocyte cultures supplemented with ORM1; however, CCL17 (a biomarker of M2a macrophages) and CXCL13 (a biomarker of M2c macrophages) were not produced in these cultures. All of these soluble factors were not detected in the culture fluids of monocytes stimulated with ORM2. Monocytes stimulated with ORM1 were characterized as CD64-CD209-CD163+CCL1+ cells. MRSA and Enterococcus faecalis infections were accelerated in chimeras (NOD/scid IL-2Rγnull mice reconstituted with white blood cells) after inoculation with monocytes stimulated with ORM1 or treatment with ORM1; however, the infections were greatly mitigated in both chimeras inoculated with ORM1-stimulated monocytes and treated with ORM1, after an additional treatment with an inhibitor of M2b macrophages (CCL1 antisense ODN). These results indicate that ORM1 stimulates quiescent monocytes to polarize to M2b monocytes. The regulation of M2b macrophages may be beneficial in controlling opportunistic infections in patients with a large amount of plasma ORM1.

Original languageEnglish (US)
Pages (from-to)8-15
Number of pages8
JournalCytokine
Volume73
Issue number1
DOIs
StatePublished - May 1 2015

Keywords

  • CCL1
  • Monocytes
  • Orosomucoid

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Hematology
  • Biochemistry
  • Molecular Biology

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