Potula Hari-Hara, Richer Luciana, Werts Catherine, Gomes-Solecki Maria
Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
Immuno Technologies Inc., Memphis, Tennessee, United States of America.
PLoS Negl Trop Dis. 2017 Aug 25;11(8):e0005870. doi: 10.1371/journal.pntd.0005870. eCollection 2017 Aug.
Recent estimates on global morbidity and mortality caused by Leptospirosis point to one million cases and almost 60,000 deaths a year worldwide, especially in resource poor countries. We analyzed how a commensal probiotic immunomodulator, Lactobacillus plantarum, affects Leptospira interrogans pathogenesis in a murine model of sub-lethal leptospirosis. We found that repeated oral pre-treatment of mice with live L. plantarum restored body weight to normal levels in mice infected with L. interrogans. Pre-treatment did not prevent L. interrogans access to the kidney but it affected the inflammatory response and it reduced histopathological signs of disease. Analysis of the immune cell profiles in lymphoid tissues of mice pre-treated with L. plantarum showed increased numbers of B cells as well as naïve and memory CD4+ helper T cell populations in uninfected mice that shifted towards increased numbers of effector CD4+ helper T in infected mice. CD8+ cytotoxic T cell profiles in pre-treated uninfected and infected mice mirrored the switch observed for CD4+ except that CD8+ memory T cells were not affected. In addition, pre-treatment led to increased populations of monocytes in lymphoid tissues of uninfected mice and to increased populations of macrophages in the same tissues of infected mice. Immunohistochemistry of kidney sections of pre-treated infected mice showed an enrichment of neutrophils and macrophages and a reduction of total leucocytes and T cells. Our results suggest that complex myeloid and T cell responses orchestrate the deployment of monocytes and other cells from lymphoid tissue and the recruitment of neutrophils and macrophages to the kidney, and that, the presence of these cells in the target organ may be associated with reductions in pathogenesis observed in infected mice treated with L. plantarum.
近期对钩端螺旋体病所致全球发病率和死亡率的估计表明,全球每年有100万例病例,近6万人死亡,尤其是在资源匮乏的国家。我们分析了一种共生益生菌免疫调节剂——植物乳杆菌,在亚致死性钩端螺旋体病小鼠模型中如何影响问号钩端螺旋体的发病机制。我们发现,用活的植物乳杆菌对小鼠进行重复口服预处理可使感染问号钩端螺旋体的小鼠体重恢复到正常水平。预处理并未阻止问号钩端螺旋体进入肾脏,但它影响了炎症反应,并减轻了疾病的组织病理学症状。对用植物乳杆菌预处理的小鼠淋巴组织中的免疫细胞谱分析显示,未感染小鼠中B细胞以及幼稚和记忆CD4+辅助性T细胞群体数量增加,而在感染小鼠中则转向效应CD4+辅助性T细胞数量增加。预处理的未感染和感染小鼠中的CD8+细胞毒性T细胞谱反映了CD4+细胞所观察到的转变,只是CD8+记忆T细胞未受影响。此外,预处理导致未感染小鼠淋巴组织中单核细胞群体增加,以及感染小鼠相同组织中巨噬细胞群体增加。对预处理的感染小鼠肾脏切片进行免疫组织化学分析显示,中性粒细胞和巨噬细胞增多,而总白细胞和T细胞减少。我们的结果表明,复杂的髓系和T细胞反应协调了单核细胞和其他细胞从淋巴组织的部署以及中性粒细胞和巨噬细胞向肾脏的募集,并且,这些细胞在靶器官中的存在可能与在用植物乳杆菌治疗的感染小鼠中观察到的发病机制减轻有关。