McClemens Jessica, Kim Janice J, Wang Huaqing, Mao Yu-Kang, Collins Matthew, Kunze Wolfgang, Bienenstock John, Forsythe Paul, Khan Waliul I
Farncombe Family Digestive Health Research Institute, Ontario, Canada.
Clin Vaccine Immunol. 2013 Jun;20(6):818-26. doi: 10.1128/CVI.00047-13. Epub 2013 Mar 27.
Enteric parasite infections around the world are a huge economic burden and decrease the quality of life for many people. The use of beneficial bacteria has attracted attention for their potential therapeutic applications in various diseases. However, the effects of beneficial bacteria in enteric parasitic infections remain largely unexplored. We investigated the effects of ingestion of Lactobacillus rhamnosus (JB-1) in a model of enteric nematode (Trichuris muris) infection. C57BL/6 (resistant to infection), AKR (susceptible to infection), interleukin 10 (IL-10) knockout (KO), and mucin Muc2 KO mice were infected with T. muris and treated orally with probiotic JB-1 or medium. The mice were sacrificed on various days postinfection to examine goblet cells, epithelial cell proliferation, cytokines, and worm burdens. Treatment with JB-1 significantly enhanced worm expulsion in resistant C57BL/6 mice, and this was associated with increases in IL-10 levels, goblet cell numbers, and epithelial cell proliferation. Beneficial effects of JB-1 were absent in IL-10 KO and resistant mice treated with γ-irradiated bacteria. Live JB-1 treatment also expedited worm expulsion in Muc2 KO mice and, more importantly, in AKR mice (susceptible to infection). Injection of IL-10 directly into the colonic tissue of uninfected mice induced goblet cell hyperplasia. These findings demonstrate that JB-1 modulates goblet cell biology and promotes parasite expulsion via an IL-10-mediated pathway and provide novel insights into probiotic effects on innate defense in nematode infection.
全球范围内的肠道寄生虫感染造成了巨大的经济负担,并降低了许多人的生活质量。有益菌因其在各种疾病中的潜在治疗应用而受到关注。然而,有益菌在肠道寄生虫感染中的作用在很大程度上仍未得到探索。我们在肠道线虫(鼠鞭虫)感染模型中研究了摄入鼠李糖乳杆菌(JB-1)的效果。将C57BL/6(对感染有抗性)、AKR(对感染易感)、白细胞介素10(IL-10)基因敲除(KO)和粘蛋白Muc2基因敲除的小鼠感染鼠鞭虫,并用益生菌JB-1或培养基进行口服治疗。在感染后的不同天数处死小鼠,以检查杯状细胞、上皮细胞增殖、细胞因子和虫负荷。用JB-1治疗显著增强了抗性C57BL/6小鼠的驱虫效果,这与IL-10水平升高、杯状细胞数量增加和上皮细胞增殖有关。在用γ射线照射过的细菌处理的IL-10基因敲除和抗性小鼠中,JB-1没有产生有益效果。活的JB-1治疗还加快了Muc2基因敲除小鼠以及更重要的是AKR小鼠(对感染易感)的驱虫速度。将IL-10直接注射到未感染小鼠的结肠组织中可诱导杯状细胞增生。这些发现表明,JB-1通过IL-10介导的途径调节杯状细胞生物学并促进寄生虫排出,并为益生菌对线虫感染先天防御的作用提供了新的见解。