Shin Min-Kyoung, Park Hongtae, Shin Seung Won, Jung Myunghwan, Lee Su-Hyung, Kim Dae-Yong, Yoo Han Sang
Department of Infectious Diseases, College of Veterinary Medicine, Seoul National University, Seoul, Korea; Department of Microbiology, Gyeonsang National University School of Medicine, Jinju, Korea.
Department of Infectious Diseases, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
PLoS One. 2015 Oct 6;10(10):e0138770. doi: 10.1371/journal.pone.0138770. eCollection 2015.
Paratuberculosis or Johne's disease is a chronic granulomatous enteropathy in ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP) infection. In the present study, we examined the host response to MAP infection in spleens of mice in order to investigate the host immunopathology accompanying host-pathogen interaction. Transcriptional profiles of the MAP-infected mice at 3 and 6 weeks p.i. showed severe histopathological changes, whereas those at 12 weeks p.i. displayed reduced lesion severity in the spleen and liver. MAP-infected mice at 3 and 6 weeks p.i. showed up-regulation of interferon-related genes, scavenger receptor, and complement components, suggesting an initial innate immune reaction, such as macrophage activation, bactericidal activity, and macrophage invasion of MAP. Concurrently, MAP-infected mice at 3 and 6 weeks p.i. were also suggested to express M2 macrophage phenotype with up-regulation of Mrc1, and Marco and down-regulation of MHC class II, Ccr7, and Irf5, and canonical pathways related to the T cell response including ICOS-ICOSL signaling in T helper cells, calcium-induced T lymphocyte apoptosis, and CD28 signaling in T helper cell. These results provide information which furthers the understanding of the immunopathologic response to MAP infection in mice, thereby providing insights valuable for research into the pathogenesis for MAP infection.
副结核病或约内氏病是由副结核分枝杆菌（MAP）感染引起的反刍动物慢性肉芽肿性肠病。在本研究中，我们检测了小鼠脾脏对MAP感染的宿主反应，以研究宿主与病原体相互作用时伴随的宿主免疫病理学。感染MAP的小鼠在感染后3周和6周时的转录谱显示出严重的组织病理学变化，而在感染后12周时，脾脏和肝脏中的病变严重程度降低。感染MAP的小鼠在感染后3周和6周时，干扰素相关基因、清道夫受体和补体成分上调，提示存在初始固有免疫反应，如巨噬细胞活化、杀菌活性以及巨噬细胞对MAP的侵袭。同时，感染MAP的小鼠在感染后3周和6周时还表现出M2巨噬细胞表型，Mrc1、Marco上调，MHC II类分子、Ccr7和Irf5下调，以及与T细胞反应相关的经典途径，包括辅助性T细胞中的ICOS-ICOSL信号传导、钙诱导的T淋巴细胞凋亡和辅助性T细胞中的CD28信号传导。这些结果提供了有助于进一步了解小鼠对MAP感染的免疫病理反应的信息，从而为MAP感染发病机制的研究提供了有价值的见解。
