Cytokine production and signalling in human THP-1 macrophages is dependent on Toxocara canis glycans

Ewa Długosz,Katarzyna Basałaj,Anna Zawistowska-Deniziak

doi:10.1007/s00436-019-06405-8

Abstract

The effect of Toxocara canis antigens on cytokine production by human THP-1 macrophages was studied in vitro. Toxocara Excretory–Secretory products (TES) and recombinant mucins (Tc-MUC-2, Tc-MUC-3, Tc-MUC-4, and Tc-MUC-5) as well as deglycosylated forms of these antigens were used in the study. TES products stimulated macrophages to produce the innate proinflammatory IL-1β, IL-6, and TNF-α cytokines regardless of the presence of glycans. Recombinant mucins induced glycan-dependent cytokine production. Sugar moieties led to at least 3-fold higher production of regulatory IL-10 as well as proinflammatory cytokines. The presence of glycans on mucins also affected the downstream signalling pathways in stimulated cells. The most prominent difference was noted in AKT and AMPK kinase activation. AKT phosphorylation was observed in cells stimulated with glycosylated mucins, whereas treatment with deglycosylated antigens led to AMPK phosphorylation. MAP kinase family members such as JNK and p38 and c-Jun transcription factor were phosphorylated in both cases what suggests that toll-like receptor signalling may be involved in mucin-treated macrophages. This pathway is however modified by other signalling molecules as only mucins containing intact sugars significantly induced the production of cytokines.

Highlights

Toxocara canis and Toxocara cati, the dog and the cat roundworm respectively, are parasitic nematodes with great zoonotic potential
We decided to analyse the effect of roundworm antigens on cytokine release by human macrophages since these cells are reliable model for other organisms (Alvarado et al 2017; Bąska et al 2017)
Macrophages are a heterogeneous group of immune cells and their phenotype and functions are regulated by the surrounding micro-environment

Summary

Introduction

Toxocara canis and Toxocara cati, the dog and the cat roundworm respectively, are parasitic nematodes with great zoonotic potential. Toxocariasis is prevalent across the globe, with children especially at risk of infection. The incidence of T. canis serum-positive individuals varies from 1.6% in Japan and 2.4% in Denmark, up to 63% in Bali, 86% in Saint-Lucia, and almost 93% in La Reunion (Magnaval et al 2001; Ma et al 2018). Upon infection of the human host, Toxocara larvae migrate through various tissues leading to different clinical syndromes: visceral larva migrans (VLM), ocular larva migrans (OLM), and Section Editor: Ramaswamy Kalyanasundaram. Toxocara worms contribute to the development of allergic diseases, including asthma, chronic urticaria, or angioedema (Magnaval et al 2001; Pinelli et al 2008)

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