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Abstract：
Understanding the determinants of host and tissue tropisms among parasites of veterinary and medical importance has long posed a substantial challenge. Among the seven species of Eimeria known to parasitize the chicken intestine, a wide variation in tissue tropisms has been observed. Prior research suggested that microneme protein (MIC) composed of microneme adhesive repeat (MAR) domain responsible for initial host cell recognition and attachment likely dictated the tissue tropism of Eimeria parasites. This study aimed to explore the roles of MICs and their associated MARs in conferring site-specific development of E. acervuline, E. maxima, and E. mitis within the host. Immunofluorescence assays revealed that MIC3 of E. acervuline (EaMIC3), MIC3 of E. maxima (EmMIC3), MIC3 of E. mitis (EmiMIC3), MAR3 of EaMIC3 (EaMIC3-MAR3), MAR2 of EmMIC3 (EmMIC3-MAR2), and MAR4 of EmiMIC3 (EmiMIC3-MAR4), exhibited binding capabilities to the specific intestinal tract where these parasites infect. In contrast, the invasion of sporozoites into host intestinal cells could be significantly inhibited by antibodies targeting EaMIC3, EmMIC3, EmiMIC3, EaMIC3-MAR3, EmMIC3-MAR2, and EmiMIC3-MAR4. Substitution experiments involving MAR domains highlighted the crucial roles of EaMIC3-MAR3, EmMIC3-MAR2, and EmiMIC3-MAR4 in governing interactions with host ligands. Furthermore, animal experiments substantiated the significant contribution of EmiMIC3, EmiMIC3-MAR4, and their polyclonal antibodies in conferring protective immunity to Eimeria-affiliated birds. In summary, EaMIC3, EmMIC3, and EmiMIC3 are the underlying factors behind the diverse tissue tropisms exhibited by E. acervuline, E. maxima, and E. mitis, and EaMIC3-MAR3, EmMIC3-MAR2, and EmiMIC3-MAR4 are the major determinants of MIC-mediated tissue tropism of each parasite. The results illuminated the molecular basis of the modes of action of Eimeria MICs, thereby facilitating an understanding and rationalization of the marked differences in tissue tropisms among E. acervuline, E. maxima, and E. mitis.
摘要：
长期以来，了解兽医和医学重要性寄生虫中宿主和组织嗜性的决定因素一直构成重大挑战。在已知寄生鸡肠的七种艾美球虫中，已观察到组织嗜性的广泛变化。先前的研究表明，由负责初始宿主细胞识别和附着的微丝粘附重复（MAR）结构域组成的微丝蛋白（MIC）可能决定了艾美球虫寄生虫的组织嗜性。本研究旨在探讨MIC及其相关的MARs在赋予E.acervuline位点特异性发育中的作用，E.最大值，和宿主内的E.mitis。免疫荧光分析显示，E.acervuline（EaMIC3）的MIC3，E.maxima的MIC3（EmMIC3），E.mitis的MIC3（EmiMIC3），EaMIC3的MAR3（EaMIC3-MAR3），EmMIC3的MAR2(EmMIC3-MAR2),和EmiMIC3的MAR4（EmiMIC3-MAR4），表现出与这些寄生虫感染的特定肠道的结合能力。相比之下,针对EaMIC3，EmMIC3，EmiMIC3，EaMIC3-MAR3，EmMIC3-MAR2和EmiMIC3-MAR4的抗体可以显着抑制子孢子对宿主肠细胞的侵袭。涉及MAR结构域的取代实验强调了EaMIC3-MAR3，EmMIC3-MAR2和EmiMIC3-MAR4在控制与宿主配体的相互作用中的关键作用。此外，动物实验证实了EmiMIC3，EmiMIC3-MAR4及其多克隆抗体在赋予艾美球虫附属鸟类保护性免疫方面的重要贡献。总之,EaMIC3，EmMIC3和EmiMIC3是E.acervuline表现出的各种组织嗜性背后的潜在因素，E.最大值，还有E.Mitis,EaMIC3-MAR3，EmMIC3-MAR2和EmiMIC3-MAR4是每种寄生虫MIC介导的组织嗜性的主要决定因素。结果阐明了艾美球虫MIC作用方式的分子基础，从而促进对E.acervuline之间组织嗜性的明显差异的理解和合理化，E.最大值，还有E.米蒂斯.
