The microneme protein1 (MIC1) of Chinese 1 Toxoplasma regulates pyroptosis through the TLR4/NLRP3 pathway in macrophages.

IF 3 2区医学 Q1 PARASITOLOGY Parasites & Vectors Pub Date : 2024-11-29 DOI:10.1186/s13071-024-06584-z

Wenze Sun, Fan Zhang, Jinjin Zhu, Yanxia Yu, Yang Wang, Qingli Luo, Li Yu

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Abstract

Background: TgMIC1, a soluble adhesion protein that typically facilitates parasite invasion, exhibited varying expression levels among distinct virulence strains of Chinese 1 Toxoplasma. This study aims to explore its role in immunological regulation and its association with diverse postinfection outcomes in Toxoplasma infection.

Methods: First, the mic1 knockout strain Wh3Δmic1 was generated and assessed for its virulence and proliferative capacity. Subsequently, the serum inflammation levels were examined in mice infected with Wh3Δmic1, Wh3, and Wh6. Furthermore, rMIC1 and rMIC1-T126A/T220A, which lack binding sites to N-glycan in TLR4, were produced for coculture with bone marrow-derived macrophages (BMDMs) to investigate their impact on pyroptosis.

Results: Our data showed Wh3Δmic1 exhibited a significant reduction in invasion efficiency, limited growth, and attenuated inflammatory responses in mice. Additionally, it displayed a decreased capacity to induce pyroptosis when compared with Wh3-infected BMDMs. Moreover, rMIC1 but not rMIC1-T126A/T220A was found to be able to upregulate NOD-like receptor pyrin domain-containing protein 3 (NLRP3) and activate GSDMD and caspase-1 in BMDMs but not in TLR4^-/- and NLRP3^-/- BMDMs.

Conclusions: TgMIC1 is implicated in both parasite invasion and the modulation of macrophage pyroptosis via the TLR4/NLRP3 pathway. This investigation indicates that TgMIC1 serves diverse functions in Toxoplasma gondii infection, thereby enhancing comprehension of the immune regulatory mechanisms of the parasite.

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来源期刊

Parasites & Vectors 医学-寄生虫学

CiteScore

6.30

自引率

9.40%

发文量

433

审稿时长

1.4 months

期刊介绍： Parasites & Vectors is an open access, peer-reviewed online journal dealing with the biology of parasites, parasitic diseases, intermediate hosts, vectors and vector-borne pathogens. Manuscripts published in this journal will be available to all worldwide, with no barriers to access, immediately following acceptance. However, authors retain the copyright of their material and may use it, or distribute it, as they wish. Manuscripts on all aspects of the basic and applied biology of parasites, intermediate hosts, vectors and vector-borne pathogens will be considered. In addition to the traditional and well-established areas of science in these fields, we also aim to provide a vehicle for publication of the rapidly developing resources and technology in parasite, intermediate host and vector genomics and their impacts on biological research. We are able to publish large datasets and extensive results, frequently associated with genomic and post-genomic technologies, which are not readily accommodated in traditional journals. Manuscripts addressing broader issues, for example economics, social sciences and global climate change in relation to parasites, vectors and disease control, are also welcomed.