Function of Neospora caninum dense granule protein 7 in innate immunity in mice
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IMMUNOLOGY AND HOST-PARASITE INTERACTIONS - ORIGINAL PAPER
Function of Neospora caninum dense granule protein 7 in innate immunity in mice Fei Wang 1 & Xianmei Wang 1 & Xingju Song 1 & Lei Ma 1 & Jing Yang 1 & Qun Liu 1,2 & Jing Liu 1,2 Received: 26 May 2020 / Accepted: 2 November 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract The intracellular parasite Neospora caninum can parasitize all nucleated cells of the host. Dense granule proteins (GRAs) secreted by dense granules are an important material involved in the formation of parasitophorous vacuoles (PVs), which facilitate parasite survival and replication in host cells. Due to the secretory and immune properties of NcGRA7, it is considered to be a promising serodiagnosis marker and an effective neosporosis vaccine candidate. However, the intracellular regulatory mechanisms involved in NcGRA7-induced host responses have rarely been examined. Here, we used the CRISPR/Cas9 genome editing system to obtain a NcGRA7 knockout strain (ΔNcGRA7) and a NcGRA7 complementary strain (iΔNcGRA7) to study their function. We found that ΔNcGRA7 exhibited slower growth in vitro and weakened virulence in mice compared with Nc1 and iΔNcGRA7. All parasite strains can stimulate host immune cells to produce IFN-γ, and the amount of IFN-γ production stimulated by Nc1 was significantly higher than that stimulated by ΔNcGRA7. The transcription levels of the cellular immune factors GBP1, GBP2, IRGa6, and IRGb6 were significantly higher after stimulation with ΔNcGRA7 parasites than after stimulation with Nc1. Furthermore, ΔNcGRA7 infection resulted in greater IRGa6 recruitment to the PVM than Nc1 infection. ΔNcGRA7 parasites were more easily cleared by macrophages than Nc1 parasites. Collectively, these results showed that NcGRA7 plays an important role in regulating the immune factors of mice and the aggregation of IRGa6 at the PVM, which affects the pathogenicity of N. caninum. Keywords Neospora caninum . Dense granule protein 7 . IRGa6 . Innate immunity
Background N. caninum is an obligate intracellular apicomplexan parasite that is similar to Toxoplasma gondii and exhibits a similar morphology, although N. caninum neither infects humans nor shares the same definitive host as T. gondii (Dubey et al. 1988; McAllister et al. 1998). Neosporosis, which is caused by N. caninum parasites, results in abortion in pregnant animals and stillbirth and neurological dysfunction in newborn animals (Dubey and Lindsay 1996; Marsh et al. 1996). Section Editor: Xing-Quan ZHU * Jing Liu [email protected] 1
National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People’s Republic of China
2
Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People’s Republic of China
Neosporosis causes considerable economic losses to the animal husbandry industry, especially cattle farms (Dubey 2003; Reichel et al. 2013). N. caninu
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