Fungal β-glucans and mannan stimulate peripheral blood mononuclear cells to cytokine production in Syk-dependent manner

Immunobiology. 2020 Sep;225(5):151985. doi: 10.1016/j.imbio.2020.151985. Epub 2020 Jul 28.

Abstract

There is evidence that major components of the fungi cell wall not only define fungal properties and survival but also are responsible for their biological activities. Some data indicate that structural components of the fungal cell wall exert stimulatory/modulatory effects on immunocompetent cells acting as pathogen-associated molecular patterns (PAMPs). Fungal components can influence the activity of certain immune cell populations by affecting cell maturation and proliferation, promoting phagocytosis, cytotoxic activity, and cell migration, as well as production of various mediators. However, there is little information available concerning the impact of fungal-derived components on peripheral blood mononuclear cell (PBMC) activation. The aim of this study was to determine whether certain fungi-associated molecules, i.e., β-(1,3)-glucans (zymosan and curdlan) and mannan activate in vitro human PBMCs to synthesize cytokines, including chemokines. We documented that PBMCs, in response to stimulation with zymosan, curdlan, and mannan, express cytokines IFN-γ and GM-CSF, and chemokine CCL3, both at protein and transcript levels, as well as cytokine IL-1β and chemokine CXCL8, at mRNA level. Our observations support the idea that fungal-derived components can activate immune cells, including PBMCs, by stimulation of cytokine/chemokine production. A thorough understanding of this interaction is of prime importance since it influence both pathophysiological and immune processes as well as anti-fungal defense mechanisms.

Keywords: Cytokine; Fungi; Mannan; PBMCs; β-glucans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Fungi
  • Glucans / pharmacology
  • Humans
  • Lectins, C-Type / antagonists & inhibitors
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / metabolism
  • Mannans / pharmacology*
  • Oxazines / pharmacology
  • Protein Kinase Inhibitors / pharmacology
  • Pyridines / pharmacology
  • RNA, Messenger / metabolism
  • Syk Kinase / antagonists & inhibitors
  • Syk Kinase / metabolism*
  • Zymosan / pharmacology*
  • beta-Glucans / pharmacology*

Substances

  • CLEC7A protein, human
  • Cytokines
  • Glucans
  • Lectins, C-Type
  • Mannans
  • N4-(2,2-dimethyl-3-oxo-4H-pyrid(1,4)oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine
  • Oxazines
  • Protein Kinase Inhibitors
  • Pyridines
  • RNA, Messenger
  • beta-Glucans
  • curdlan
  • laminaran
  • Zymosan
  • SYK protein, human
  • Syk Kinase