Dectin-1 on macrophages modulates the immune response to Fasciola hepatica products through the ERK signaling pathway

Immunobiology. 2018 Dec;223(12):834-838. doi: 10.1016/j.imbio.2018.08.004. Epub 2018 Aug 10.

Abstract

Fasciolosis is a zoonotic disease of increasing importance due to its worldwide distribution and elevated economic losses. Previously, we demonstrated that Fasciola hepatica excretory-secretory products (FhESP) induce immunomodulatory effects on peritoneal macrophages in a Dectin-1 dependent manner. In this study, we observed that peritoneal macrophages from naive BALB/c mice stimulated in vitro with FhESP presented increased expression levels of phosphorylated extracellular-signal-regulated kinase (ERK), and this effect was dependent on Syk, protein kinase C (PKC) and Dectin-1. In this sense, we observed increased levels of arginase activity, IL-10 and TGF-β in macrophages stimulated with FhESP, which were dependent on PKC and ERK. Furthermore, we observed that the increased arginase activity, as well as in TGF-β and IL-10 levels, was partially dependent on IL-10 receptor signaling in macrophages that were pre-incubated with anti-IL10R before being stimulated with FhESP. Taken together, these results suggest the participation of Dectin-1 and Syk in FhESP interaction with peritoneal macrophages and the possible role of ERK and IL-10 in downstream signaling pathways involved in the immunomodulatory effects induced by Fasciola hepatica products.

Keywords: Dectin-1; Excretory-secretory products; Fasciola hepatica; Macrophage immunomodulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginase / metabolism
  • Cytokines / biosynthesis
  • Enzyme Activation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fasciola hepatica / immunology*
  • Fascioliasis / immunology*
  • Fascioliasis / metabolism
  • Fascioliasis / parasitology*
  • Female
  • Immunomodulation*
  • Lectins, C-Type / metabolism*
  • MAP Kinase Signaling System*
  • Macrophages / immunology*
  • Macrophages / metabolism*
  • Mice
  • Phosphorylation

Substances

  • Cytokines
  • Lectins, C-Type
  • dectin 1
  • Extracellular Signal-Regulated MAP Kinases
  • Arginase