Effect of Imiquimod on Tachyzoites of Toxoplasma gondii and Infected Macrophages in vitro and in BALB/c Mice

Abstract

Treatment for toxoplasmosis is not completely successful because of their unwanted side effects, and new treatments are needed. Imiquimod has ability to moderate immune response and used to treat a wide variety of infections and tumors. The aim of the present study was to evaluate the effect of imiquimod on the tachyzoites of T. gondii and infected macrophages in vitro and in BALB/c mice. The viability of T. gondii was assessed in the presence of various concentrations of imiquimod by direct counting after 6 and 24 h. The MTT assay was used to identify the viability of uninfected macrophages. The apoptotic effects were determined with flow cytometry on the tachyzoites and infected macrophages. For evaluation of parasite load in pre-treatment or post-treatment of macrophages Quantitative real time PCR (qPCR) was performed. For in vivo experiments, BALB/c mice received imiquimod before and after challenge with parasites. The mortality rate of mice, parasite numbers in spleen, and the INF-γ and IL-4 cytokine levels in spleen lymphocytes were evaluated. Imiquimod demonstrated anti-Toxoplasma effects by reducing the number of tachyzoites. The results of flow cytometry for drug-treated tachyzoites showed that apoptosis did not rise significantly relative to the control group (p < 0.05). Moreover, apoptosis was enhanced in infected macrophages as the concentration of imiquimod was reduced. The parasitic burden in imiquimod pretreated macrophages was significantly lower than those treated after infection (p < 0.01). A marked reduction was observed in survival rate, parasite load and INF-γ level in BALB/c mice that received imiquimod before parasitic challenge relative to those received drug after parasitic challenge (p < 0.01). Overall, imiquimod in the pretreated group had greater anti-Toxoplasma effects than imiquimod in posttreated group in vitro and in vivo. imiquimod may be considered as a candidate for use against Toxoplasmosis both therapeutically and prophylactically.

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

“…In vitro , Imiquimod led to a pronounced effect against tachyzoïtes in infected macrophages. This result is consistent with the recent work by ( 39 ). In vivo , Imiquimod reduced tachyzoïte burden in the spleen, likely as a consequence to the increase of CD11b positive innate immune cells.…”

“…Furthermore, Imiquimod proved potent and safe when used as simple vaccine adjuvant in mice ( 75 ). In the context of toxoplasmosis, and using a type I virulent strain, Imiquimod showed promising prophylactic and therapeutic activities against acute toxoplasmosis in BALB/c mice ( 39 ). Yet, the virulent type I strains do not allow studying chronic toxoplasmosis, which the most common form of the disease in intermediate hosts, including humans.…”

“…Recently, Imiquimod demonstrated anti-Toxoplasma effects in vitro, and in vivo using a type I virulent strain. In addition, mice prophylactically pre-treated with imiquimod, before infection, showed prolonged survival time compared with post-treated and control groups, highlighting a prophylactic potency of this drug against toxoplasmosis (39). Imiquimod binds Toll-like receptor-7 (TLR-7) (40,41), and activates the innate immune response through MyD88 signaling pathway (41).…”

Echinococcus multilocularis drives the polarization of macrophages by regulating the RhoA-MAPK signaling pathway and thus affects liver fibrosis

“…Macrophage polarization is related to parasitic infections. Macrophage polarization has been examined in mice with infection by schistosoma [ 19 ] and has also been reported in other parasitic diseases induced by toxoplasma gondii [ 20 ] and Clonorchis sinensis [ 21 ]. Macrophage polarization is associated with alveolar echinococcosis infection [ 22 ].…”

Global prevalence of Toxoplasma gondii in birds: A systematic review and meta-analysis

“…The protozoan Toxoplasma gondii ( T. gondii ), the causative agent of toxoplasmosis, is one of the most successful parasites and can infect humans and almost all warm-blooded animals globally Dubey et al, 2020 ; Zaki et al, 2020a ; Abbasali et al, 2023 ). It is a major public health issue, and it is estimated that nearly a third of the world's human population is infected ( Dubey, 2008 ; Dubey et al, 2020 ).…”