Soluble total antigen derived from Toxoplasma gondii tachyzoites increased the expression levels of NLRP1, NLRP3, NLRC4, AIM2, and the release of mature form of IL1β, but downregulated the expression of IL1β and IL18 genes in THP-1cell line.

Toxoplasma gondii (T. gondii) is an intracellular parasitic protozoan infecting homoeothermic animals and about a third of the world's population. Inflammasomes are intracellular multi-protein complex, which are activated by many factors. Inflammasomes are activated during toxoplasmosis; however, there are a lot of obscure aspects. THP-1 monocyte cells were converted to M0 macrophages by PMA and treated by 100 μg/mL soluble total Ag (STAg) derived from T. gondii strain RH for two time points 3 h and 24 h. After total RNA extraction and cDNA synthesis, the expression pattern of NLRP1, NLRP3, NLRC4, AIM2, IL1β, and IL18 was evaluated by relative real-time PCR. In addition, the cytokine release of IL1β and TNFα was evaluated in the supernatant of each well. The results showed statistically significant time-dependent overexpression of inflammasomes. NLRP1 and NLRP3 showed the higher and lower expression, respectively, during 3 h and 24 h after exposure. Both IL1β and IL18 downregulated 3 h after exposure. IL18 presented statistically significant upregulation after 24 h, but IL1β showed statistically significant downregulation after 24 h. The release of IL1β increased after 3 h, but it slightly decreased during 24 h after exposure. The concentration of TNFα showed an insignificant decrease compared to control, while it increased during 24 h after exposure. Taken together, this study suggested that T. gondii STAg induces NLRP1 more than NLRP3, NLRC4, and AIM2. Our findings also proposed that T. gondii STAg downregulates the gene expression of IL1β, but increases the release of this cytokine. It seems that Toxoplasma STAg probably increase the release of IL1β via activating NLRPs and AIM2 to cleave pro-caspase 1 to caspase 1 that leads to conversion of pro IL1β to mature IL1β. Copyright © 2021 Elsevier Ltd. All rights reserved.

Citation

Hossein Pazoki, Hanieh Mohammad Rahimi, Hamed Mirjalali, Maryam Niyyati, Nariman Mosaffa, Seyed Javad Seyed Tabaei, Shabnam Shahrokh, Hamid Asadzadeh Aghdaei, Mohammad Reza Zali. Soluble total antigen derived from Toxoplasma gondii tachyzoites increased the expression levels of NLRP1, NLRP3, NLRC4, AIM2, and the release of mature form of IL1β, but downregulated the expression of IL1β and IL18 genes in THP-1cell line. Microbial pathogenesis. 2021 Sep;158:105072

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PMID: 34192597

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