Imiquimod Targets Toxoplasmosis Through Modulating Host Toll-Like Receptor-MyD88 Signaling.

Maguy Hamie,Rania Najm,Marwan El Sabban,Pierre Antoine Bonnet,Hiba El Hajj,Carine Deleuze-Masquefa,Jean-François Dubremetz

doi:10.3389/fimmu.2021.629917

Abstract

Toxoplasma gondii is a prevalent parasite of medical and veterinary importance. Tachyzoïtes and bradyzoïtes are responsible for acute and chronic toxoplasmosis (AT and CT), respectively. In immunocompetent hosts, AT evolves into a persistent CT, which can reactivate in immunocompromised patients with dire consequences. Imiquimod is an efficient immunomodulatory drug against certain viral and parasitic infections. In vivo, treatment with Imiquimod, throughout AT, reduces the number of brain cysts while rendering the remaining cysts un-infectious. Post-establishment of CT, Imiquimod significantly reduces the number of brain cysts, leading to a delay or abortion of reactivation. At the molecular level, Imiquimod upregulates the expression of Toll-like receptors 7, 11, and 12, following interconversion from bradyzoïtes to tachyzoïtes. Consequently, MyD88 pathway is activated, resulting in the induction of the immune response to control reactivated Toxoplasma foci. This study positions Imiquimod as a potent drug against toxoplasmosis and elucidates its mechanism of action particularly against chronic toxoplasmosis, which is the most prevalent form of the disease.

Highlights

Toxoplasma gondii (T. gondii) is the etiologic agent of toxoplasmosis, a common human and zoonotic disease
Imiquimod Is Effective on Toxoplasma gondii Tachyzoites in vitro and in vivo We investigated the potency of Imiquimod on macrophages infected with tachyzoïte stage of the 76K strain of T. gondii
Imiquimod significantly reduced the expression of the tachyzoïte-specific protein surface antigen 1 (SAG-1) (Figure 1A)

Summary

Introduction

Toxoplasma gondii (T. gondii) is the etiologic agent of toxoplasmosis, a common human and zoonotic disease. T. gondii infects ∼30% of the world’s human population [1], with a seroprevalence that can reach 80% in some regions [2]. Toxoplasmosis was classified by the Centers for Disease Control and Prevention as a neglected parasitic infection, requiring public health action [3]. While toxoplasmosis is considered asymptomatic in most immunocompetent patients, several medical conditions are associated with T. gondii infection [8]. Higher antibody titers against T. gondii are reported in different types of cancers [11,12,13], in brain cancers due to the ability of the parasite to interfere with the brain cells miRNAome [14].

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Conclusion