Pazoki, Hossein, Mirjalali, Hamed, Niyyati, Maryam, Seyed Tabaei, Seyed Javad, Mosaffa, Nariman, Shahrokh, Shabnam, Asadzadeh Ahdaei, Hamid, Kupz, Andreas, and Zali, Mohammad Reza (2023) Toxoplasma gondii profilin induces NLRP3 activation and IL-1β production/secretion in THP-1 cells. Microbial Pathogenesis, 180. 106120.

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Abstract

Toxoplasma gondii is a highly prevalent protozoan that infects a broad spectrum of warm-blooded animals. Profilin is a critical protein that plays a role in the movement and invasion of T. gondii. In the current study, we assessed how profilin stimulates inflammasomes and how it induces transcription and secretion of IL-1β. For this purpose, we assessed the level of TLR 2, 4, 5, and 9 expressions in a THP-1 cell line treated with profilin from T. gondii (TgP). In addition, we analyzed the expression levels of various inflammasomes, as well as IL-1β, and IL-18 in THP-1 cells treated with the NLRP3 inhibitor MCC950. TgP significantly increased the expression of TLR5 but the expression of TLR2, 4, and 9 was not significantly increased. In addition, TgP did not significantly increase the level of inflammasomes after 5 h. Treatment with MCC950 significantly reduced NLRP3 and IL-1β on both transcription and protein levels. Although the transcription level of NLRP3 was reduced 5 h after treatment with TgP, western blot analysis showed an increase in NLRP3. The western blot and ELISA analysis also showed that TgP increased both pro- and mature IL-1β. In summary, our study showed that NLRP3 most probably plays a pivotal role in the expression and production levels of IL-1β during the interaction between TgP and macrophages.

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