Animal, Plant and Fisheries Quarantine and Inspection Agency, Anyang, Gyunggi-do, Republic of Korea.
Viral Immunol. 2013 Jun;26(3):192-200. doi: 10.1089/vim.2012.0091. Epub 2013 May 8.
Lymphoid organs play an important role in prion disease development and progression. While the role of lymphoid organs and changes in immune-related genes have been extensively investigated in scrapie-infected animals, innate immunity has not. Previous studies examined lymphocyte function in scrapie-infected C3H/HeJ mice, which exhibit defects in lipopolysaccharide (LPS) response now known to result from a mutation in Toll-like receptor (TLR) 4. We examined immune function in scrapie-infected CD1 mice, which are LPS responders. Lymphocyte proliferation from CD1 mice infected with either 139A or ME7 scrapie was measured in response to concanavalin (Con) A or LPS at 1 and 3 months after infection. Following LPS exposure, mice infected 3 months with ME7, but not 139A, demonstrated significantly decreased lymphocyte proliferation compared to controls. After Con A exposure, lymphocyte proliferation in scrapie-infected mice did not differ from controls. Gender-specific comparison of lymphocyte proliferation showed significant decreases in mitogenic responses in females infected 3 months with either 139A or ME7, compared to controls. Males infected for 3 months with ME7, but not 139A, showed significantly decreased proliferation after lymphocyte exposure to LPS, but not Con A. Neither gender showed changes in lymphocyte proliferation after 1 month of scrapie infection. Innate immune activation of peritoneal macrophages was determined via production of nitric oxide (NO), IL-6, and TNF-α after exposure to TLR ligands. TNF-α and IL-6 production were reduced in macrophages from females infected with either scrapie strain for 3 months, while NO production after TLR agonist plus IFN-γ exposure was decreased in both females and males infected for 3 months with 139A, compared to ME7. These data demonstrated altered innate immunity, suggesting hormonal and/or other gender-specific regulation may contribute to gender differences in some immune functions. Our data demonstrate lymphocyte proliferation and innate immune functioning in scrapie-infected mice deteriorate with disease progression.
淋巴器官在朊病毒病的发展和进展中起着重要作用。虽然在感染瘙痒病的动物中已经广泛研究了淋巴器官的作用和与免疫相关的基因变化，但先天免疫尚未得到研究。以前的研究检查了感染瘙痒病的 C3H/HeJ 小鼠中的淋巴细胞功能，该小鼠表现出脂多糖（LPS）反应缺陷，现在已知该缺陷是由于 Toll 样受体（TLR）4 突变引起的。我们检查了感染瘙痒病的 CD1 小鼠的免疫功能，该小鼠对 LPS 有反应。在感染后 1 个月和 3 个月，用刀豆球蛋白 A（ConA）或 LPS 测量感染 139A 或 ME7 瘙痒病的 CD1 小鼠的淋巴细胞增殖。在 LPS 暴露后，与对照相比，感染 ME7 但未感染 139A 的 3 个月感染的小鼠的淋巴细胞增殖显著降低。在用 ConA 暴露后，感染瘙痒病的小鼠的淋巴细胞增殖与对照没有差异。淋巴细胞增殖的性别特异性比较显示，与对照相比，感染 139A 或 ME7 的雌性感染 3 个月后的有丝分裂反应明显降低。感染 ME7 但未感染 139A 的雄性感染 3 个月后的 LPS 暴露后淋巴细胞增殖明显降低，但 ConA 则不然。在感染瘙痒病 1 个月后，无论是男性还是女性，其淋巴细胞增殖均未发生变化。通过暴露于 TLR 配体后产生的一氧化氮（NO）、IL-6 和 TNF-α 来确定腹腔巨噬细胞的先天免疫激活。感染瘙痒病 3 个月后，两种瘙痒病株感染的雌性巨噬细胞中 TNF-α 和 IL-6 的产生减少，而感染 139A 的雌性和雄性巨噬细胞在 TLR 激动剂加 IFN-γ 暴露后产生的 NO 减少，与 ME7 相比。这些数据表明先天免疫发生改变，表明激素和/或其他性别特异性调节可能导致某些免疫功能的性别差异。我们的数据表明，随着疾病的进展，感染瘙痒病的小鼠的淋巴细胞增殖和先天免疫功能恶化。
