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经口途径感染小鼠的布鲁氏菌 melitensis 及其脂多糖的免疫发病机制建模。

Modelling the immunopathophysiology of Brucella melitensis and its lipopolysaccharide in mice infected via oral route of exposure.

机构信息

Department of Veterinary Clinical Studies, Faculty of Veterinary Medicine, Universiti Malaysia Kelantan, Pengkalan Chepa, 16100, Kota Bharu, Kelantan, Malaysia; Department of Veterinary Clinical Studies, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.

Department of Preclinical Studies, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.

出版信息

Microb Pathog. 2019 Nov;136:103669. doi: 10.1016/j.micpath.2019.103669. Epub 2019 Aug 21.

DOI:10.1016/j.micpath.2019.103669
PMID:31445124
Abstract

Brucella melitensis is one of the leading zoonotic pathogens with significant economic implications in animal industry worldwide. Lipopolysaccharide, however, remains by far the major virulence with substantial role in diseases pathogenesis. Nonetheless, the effect of B. melitensis and its lipopolysaccharide on immunopathophysiological aspects largely remains an enigma. This study examines the effect of B.melitensis and its lipopolysaccharide on immunopathophysiological parameters following experimental infection using mouse model. Eighty four (n = 84) mice, BALB/c, both sexes with equal gender distribution and 6-8 weeks-old were randomly assigned into three groups. Group 1-2 (n = 72) were orally inoculated with 0.4 mL containing 10 CFU/mL of B. melitensis and its LPS, respectively. Group 3 (n = 12) was challenged orally with phosphate buffered saline and served as a control group. Animals were observed for clinical signs, haematological and histopathological analysis for a period of 24 days post-infection. We hereby report that B.melitensis infected group demonstrated significant clinical signs and histopathological changes than LPS infected group. However, both infected groups showed elevated levels of interleukins (IL-1β and IL-6) and antibody levels (IgM and IgG) with varying degrees of predominance in LPS infected group than B. melitensis infected group. For hormone analysis, low levels of progesterone, estradiol and testosterone were observed in both B. melitensis and LPS groups throughout the study period. Moreover, in B. melitensis infected group, the organism was re-isolated from the organs and tissues of gastrointestinal, respiratory and reproductive systems thereby confirming the infection and transmission dynamics. This report is the first detailed investigation comparing the infection progression and host responses in relation to the immunopathophysiological aspects in a mouse model after oral inoculation with B. melitensis and its lipopolysaccharide.

摘要

贝氏疏螺旋体是一种主要的人畜共患病病原体,在全球动物产业中具有重要的经济意义。然而,脂多糖仍然是迄今为止主要的毒力因子,在疾病发病机制中起着重要作用。尽管如此,贝氏疏螺旋体及其脂多糖对免疫病理生理方面的影响在很大程度上仍然是一个谜。本研究通过小鼠模型实验感染,研究了贝氏疏螺旋体及其脂多糖对免疫病理生理参数的影响。84 只(n=84)BALB/c 雌雄各半、6-8 周龄的小鼠被随机分为三组。第 1-2 组(n=72)分别口服接种含有 10 CFU/mL 的贝氏疏螺旋体及其脂多糖的 0.4 mL 溶液。第 3 组(n=12)口服接种磷酸盐缓冲液作为对照组。感染后 24 天内观察动物的临床症状、血液学和组织病理学分析。我们报告称,贝氏疏螺旋体感染组表现出明显的临床症状和组织病理学变化,比脂多糖感染组更为严重。然而,与贝氏疏螺旋体感染组相比,两组感染组的白细胞介素(IL-1β和 IL-6)和抗体水平(IgM 和 IgG)均升高,且脂多糖感染组升高程度更大。激素分析显示,在整个研究期间,两组(贝氏疏螺旋体和脂多糖组)的孕激素、雌二醇和睾酮水平均较低。此外,在贝氏疏螺旋体感染组中,该生物体从胃肠道、呼吸道和生殖系统的器官和组织中重新分离出来,从而证实了感染和传播动力学。本报告是首次详细研究比较了在口服接种贝氏疏螺旋体及其脂多糖后,在小鼠模型中与免疫病理生理方面相关的感染进展和宿主反应。

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