Triggering Dectin-1-Pathway Alone Is Not Sufficient to Induce Cytokine Production by Murine Macrophages

PLoS One. 2016 Feb 3;11(2):e0148464. doi: 10.1371/journal.pone.0148464. eCollection 2016.

Abstract

β-glucans (BG) are abundant polysaccharides of the Saccharomyces cerevisiae cell wall (Sc CW), an industry byproduct. They have immuno-stimulatory properties upon engagement of dectin-1 (Clec7a), their main receptor on particular immune cells, and they actually become of great interest because of their preventive or therapeutic potentials. Zymosan, a crude extract of Sc CW was studied as a prototypic BG, despite its miscellaneous PAMPs content. Here, we examined the response of murine wild type or Clec7a-/- bone marrow-derived macrophages (BMDM) to products with increasing BG content (15, 65 or 75%) and compared their effects with those of other dectin-1 ligands. The enrichment process removed TLR ligands while preserving dectin-1 activity. The most enriched extracts have very low NFκB activity and triggered low amounts of cytokine production in contrast with crude products like zymosan and BG15. Furthermore, MyD88-/- BMDM did not produce TNFα in response to crude Sc CW extracts, whereas their response to BG-enriched extracts was unaffected, suggesting that BG alone are not able to initiate cytokine secretion. Although Sc CW-derived BG stimulated the late and strong expression of Csf2 in a dectin-1-dependent manner, they remain poor inducers of chemokine and cytokine production in murine macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Transformed
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis*
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Humans
  • Lectins, C-Type / biosynthesis*
  • Lectins, C-Type / genetics
  • Macrophages / cytology
  • Macrophages / metabolism*
  • Mice
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / genetics
  • Signal Transduction*
  • Zymosan / pharmacology

Substances

  • Lectins, C-Type
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • dectin 1
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Zymosan

Grant support

This work was partly financed by Phileo-Lesaffre Animal Care. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Other sources of funding were from Institut National de la Recherche Agronomique (INRA) and Institut National Polytechnique - Ecole Nationale Vétérinaire de Toulouse (INP-ENVT).