Wang Xianmei, Tang Di, Wang Fei, Jin Gaowei, Wang Lifang, Liu Qun, Liu Jing
National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Pathogens. 2021 Feb 13;10(2):201. doi: 10.3390/pathogens10020201.
, is the etiological agent of neosporosis, an infection that causes abortions in cattle and nervous system dysfunction in dogs. Invasion and egress are the key steps of the pathogenesis of infection. Microneme proteins (MICs) play important roles in the recognition, adhesion, and invasion of host cells in other apicomplexan parasites. However, some MICs and their functions in infection have rarely been reported.
The homologous recombination strategy was used to investigate the function of MIC6 in infection.
ΔNcMIC6 showed a smaller plaque size and weakened capacities of invasion and egress than Nc1. Transcription levels of the egress-related genes CDPK1, PLP1, and AMA1 of ΔNcMIC6 were downregulated. Due to the lack of NcMIC6, virulence of the pathogen in the infected mouse was weakened. The subcellular localization of NcMIC1 and NcMIC4 in ΔNcMIC6, however, did not change. Nevertheless, the transcription levels of MIC1 and MIC4 in ΔNcMIC6 were downregulated, and the expression and secretion of MIC1 and MIC4 in ΔNcMIC6 were reduced compared with that in Nc1. Furthermore, the absence of NcMIC6 weakened the virulence in mice and lower parasite load detected in mice brains.
NcMIC6 is involved in host cell invasion and egress in and may work synergistically with other MICs to regulate the virulence of the pathogen. These data lay a foundation for further research into the function and application of NcMIC6.
新孢子虫是新孢子虫病的病原体,该感染可导致牛流产和犬神经系统功能障碍。入侵和逸出是新孢子虫感染发病机制的关键步骤。微线体蛋白(MICs)在其他顶复门寄生虫对宿主细胞的识别、黏附和入侵中起重要作用。然而,一些MICs及其在新孢子虫感染中的功能鲜有报道。
采用同源重组策略研究MIC6在新孢子虫感染中的功能。
与Nc1相比,ΔNcMIC6的噬斑尺寸更小,入侵和逸出能力减弱。ΔNcMIC6的逸出相关基因CDPK1、PLP1和AMA1的转录水平下调。由于缺乏NcMIC6,病原体在感染小鼠中的毒力减弱。然而,ΔNcMIC6中NcMIC1和NcMIC4的亚细胞定位没有改变。尽管如此,ΔNcMIC6中MIC1和MIC4的转录水平下调,与Nc1相比,ΔNcMIC6中MIC1和MIC4的表达和分泌减少。此外,NcMIC6的缺失减弱了小鼠的毒力,并降低了在小鼠脑中检测到的寄生虫载量。
NcMIC6参与新孢子虫对宿主细胞的入侵和逸出,可能与其他MICs协同作用以调节病原体的毒力。这些数据为进一步研究NcMIC6的功能和应用奠定了基础。