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The role of macrophage reprogramming induced by GRA15II, a polypeptide effector molecule of Toxoplasma gondii, in liver diseases in model mice

Cellular & Molecular Immunology volume 17, pages 788–790 (2020)Cite this article

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Toxoplasma gondii is a widespread parasite that may infect nearly all warm-blooded vertebrates.1 As an obligatory intracellular apicomplexan parasite, T. gondii has three different types of secretory organelles, including micronemes, rhoptries (ROP), and dense granules (GRAs), during invasion of host cells.2 Initially, the parasite replicates in a variety of host cell types as tachyzoites, especially in macrophages and dendritic cells (DCs). Following a potent host immune response, the parasite differentiates into a slow-growing bradyzoite, which may persist as tissue cysts and escape host immune killing, resulting in sustained chronic infection. It is known that T. gondii effector proteins contribute to the construction of immune networks in host cells by interacting with host signaling pathways or altering host transcription factors. GRA15 is a crucial effector of type II strains of T. gondii that is closely associated with host immune modulation by suppressing the IDO1-dependent immune response in human neurons.3 Recent studies showed that GRA15 also inhibits IFN-γ-induced indole-2-3-dioxygenase 1-dependent antiparasitic immune responses in human cells, suggesting a novel therapeutic strategy for human toxoplasmosis by blocking NO or IL-1β production.4

Based on genetic diversity, strains of T. gondii isolated from animals and humans are divided into three archetypal lineages in Europe and North America. Type II is most commonly found in human infections of immunocompromised individuals and congenitally infected children. Type I is relatively rare in humans, while type III is common in domestic and wild animals. The Chinese 1 type, however, is a predominant lineage circulating in humans and animals in mainland China. Next-generation sequencing and genetic function studies have revealed that genotype-associated secretory/excretory proteins are involved in parasite invasion, immune evasion, host modulation, and pathogenesis during Toxoplasma infection. Macrophages and DCs undergo designated reprogramming through the corresponding transcriptional machinery when infected with a strain of a given Toxoplasma genotype.5

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Acknowledgements

We thank Michael Powers (Oakland University, MI, USA) for editing the language in the manuscript. The work was funded by the Natural Science Foundation of China (Y.C., Grant no. 81572801 and L.Y., Grant no. 81572022) and the Postdoctoral Foundation of Anhui Province (Y.C., Grant no. 2017B160).

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Authors and Affiliations

  1. Department of Health Inspection and Quarantine, School of Public Health, Anhui Medical University, Hefei, China

    Yihong Cai, Yanxia Yu, Yanling Wang & Yuan Zhang

  2. Department of Microbiology and Parasitology, the Provincial Laboratory of Pathogen Biology of Anhui, and the Key Laboratory of Zoonoses of Anhui, Anhui Medical University, Hefei, China

    Yihong Cai, Yanxia Yu, Yanling Wang, Yuan Zhang, Qingli Luo, Li Yu, Jian Du, Deyong Chu & Jilong Shen

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Contributions

Y.H.C.: study conception and design, analysis and interpretation of data, and drafting of the article. J.L.S.: conception and design of study, and editing of the article. Y.X.Y., Y.L.W., and Y.Z.: analysis and interpretation of data. Q.L.L., L.Y., J.D., and D.Y.C.: acquisition of data and drafting the article.

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Correspondence to Jilong Shen.

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Cai, Y., Yu, Y., Wang, Y. et al. The role of macrophage reprogramming induced by GRA15II, a polypeptide effector molecule of Toxoplasma gondii, in liver diseases in model mice. Cell Mol Immunol 17, 788–790 (2020). https://doi.org/10.1038/s41423-020-0422-y

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