Colinot Darrelle L, Garbuz Tamila, Bosland Maarten C, Wang Liang, Rice Susan E, Sullivan William J, Arrizabalaga Gustavo, Jerde Travis J
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana.
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana.
Prostate. 2017 Jul;77(10):1066-1075. doi: 10.1002/pros.23362. Epub 2017 May 12.
Inflammation is the most prevalent and widespread histological finding in the human prostate, and associates with the development and progression of benign prostatic hyperplasia and prostate cancer. Several factors have been hypothesized to cause inflammation, yet the role each may play in the etiology of prostatic inflammation remains unclear. This study examined the possibility that the common protozoan parasite Toxoplasma gondii induces prostatic inflammation and reactive hyperplasia in a mouse model.
Male mice were infected systemically with T. gondii parasites and prostatic inflammation was scored based on severity and focality of infiltrating leukocytes and epithelial hyperplasia. We characterized inflammatory cells with flow cytometry and the resulting epithelial proliferation with bromodeoxyuridine (BrdU) incorporation.
We found that T. gondii infects the mouse prostate within the first 14 days of infection and can establish parasite cysts that persist for at least 60 days. T. gondii infection induces a substantial and chronic inflammatory reaction in the mouse prostate characterized by monocytic and lymphocytic inflammatory infiltrate. T. gondii-induced inflammation results in reactive hyperplasia, involving basal and luminal epithelial proliferation, and the exhibition of proliferative inflammatory microglandular hyperplasia in inflamed mouse prostates.
This study identifies the common parasite T. gondii as a new trigger of prostatic inflammation, which we used to develop a novel mouse model of prostatic inflammation. This is the first report that T. gondii chronically encysts and induces chronic inflammation within the prostate of any species. Furthermore, T. gondii-induced prostatic inflammation persists and progresses without genetic manipulation in mice, offering a powerful new mouse model for the study of chronic prostatic inflammation and microglandular hyperplasia.
炎症是人类前列腺中最普遍且广泛存在的组织学表现，与良性前列腺增生和前列腺癌的发生及进展相关。已有多种因素被推测可引发炎症，但每种因素在前列腺炎症病因中所起的作用仍不明确。本研究在小鼠模型中探究了常见原生动物寄生虫弓形虫诱发前列腺炎症和反应性增生的可能性。
雄性小鼠经全身感染弓形虫寄生虫，根据浸润白细胞的严重程度和局灶性以及上皮增生情况对前列腺炎症进行评分。我们通过流式细胞术对炎症细胞进行表征，并通过溴脱氧尿苷（BrdU）掺入法对由此产生的上皮增殖进行表征。
我们发现弓形虫在感染的前14天内感染小鼠前列腺，并可形成持续至少60天的寄生虫囊肿。弓形虫感染在小鼠前列腺中诱发大量慢性炎症反应，其特征为单核细胞和淋巴细胞浸润。弓形虫诱导的炎症导致反应性增生，包括基底和管腔上皮增殖，并在发炎的小鼠前列腺中出现增殖性炎性微腺泡增生。
本研究确定常见寄生虫弓形虫为前列腺炎症的新触发因素，我们借此建立了一种新型的前列腺炎症小鼠模型。这是首份关于弓形虫在任何物种的前列腺内长期形成囊肿并诱发慢性炎症的报告。此外，在小鼠中，弓形虫诱导的前列腺炎症在未经基因操作的情况下持续存在并进展，为慢性前列腺炎症和微腺泡增生的研究提供了一个强大的新小鼠模型。
