Toxoplasma gondii tachyzoite-extract acts as a potent immunomodulator against allergic sensitization and airway inflammation

Mirjana Drinić,Christian Zwicker,Irma Schabussova,Roman Peschke,Angelika Wagner,Ursula Wiedermann,Gerhard Loupal,Elke Korb,Priya Sarate,Anja Joachim

doi:10.1038/s41598-017-15663-4

Abstract

Epidemiological and experimental studies have shown an inverse relationship between infections with certain parasites and a reduced incidence of allergic diseases. We and others have shown that infection with Toxoplasma gondii prevents the development of allergy in mice. To establish whether this beneficial effect could be recapitulated by soluble products of this parasite, we tested an extract derived from T. gondii tachyzoites. Immunization of BALB/c mice with tachyzoites lysate antigen (TLA) elicited mixed Th1/Th2 responses. When TLA was applied together with the sensitizing ovalbumin (OVA), the development of allergic airway inflammation was reduced, with decreased airway hyperresponsiveness associated with reduced peribronchial and perivascular cellular infiltration, reduced production of OVA-specific Th2 cytokines in lungs and spleens and reduced levels of serum OVA-specific IgG1 as well as IgE-dependent basophil degranulation. Of note, TLA retained its immunomodulatory properties, inducing high levels of IL-6, TNFα, IL-10 and IL-12p70 in bone marrow-derived dendritic cells after heat-inactivation or proteinase K-treatment for disruption of proteins, but not after sodium metaperiodate-treatment that degrades carbohydrate structures, suggesting that carbohydrates may play a role in immunomodulatory properties of TLA. Here we show that extracts derived from parasites may replicate the benefits of parasitic infection, offering new therapies for immune-mediated disorders.

Highlights

The prevalence of allergic, inflammatory and autoimmune diseases has been increasing in industrialized countries in the last few decades[1]
tachyzoites lysate antigen (TLA)-immunization led to significant production of TLA-specific IgG2a (Th1-associated isotype), as well as TLA-specific IgG1 (Th2-associated isotype) when compared to levels in pre-immune serum collected on day 0 and to levels in serum of sham-treated mice collected on day 21 (Fig. 2b)
Restimulation of spleen cells from TLA-immunized mice with TLA ex vivo led to increased levels of Th1-related cytokines IL-6, IFNγ and TNFα, as well as Th2 cytokines IL-5 and IL-4 and regulatory IL-10 compared to cultures incubated with medium only

Summary

Introduction

The prevalence of allergic, inflammatory and autoimmune diseases has been increasing in industrialized countries in the last few decades[1] This trend has been correlated with lifestyle changes, such as increase in hygiene measures, the wide use of antibiotics, vaccinations, as well as reduced exposure to different infectious agents, such as bacteria, protozoa and helminths[2,3,4]. There is an interest in identifying parasite-derived molecules to treat immune-mediated diseases or to use them as adjuvants with immunomodulatory effects in future allergy vaccines. We have shown that the infection with live T. gondii, and the treatment with crude extract derived from T. gondii oocysts (OLA) can reduce the development of allergic responses in a mouse model of birch pollen allergy[26]. TLA is a mixture of proteins and carbohydrates[30,31,32] and the identification of specific suppressive factors in TLA may lead to development of novel therapeutic applications to control immune-mediated inflammatory diseases

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