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Susceptibility of aging mice to listeriosis: Role of anti-inflammatory responses with enhanced Treg-cell expression of CD39/CD73 and Th-17 cells.
International Journal of Medical Microbiology ( IF 4.5 ) Pub Date : 2020-01-16 , DOI: 10.1016/j.ijmm.2020.151397
M Samiul Alam 1 , Christopher Cavanaugh 1 , Marion Pereira 1 , Uma Babu 1 , Kristina Williams 1
Affiliation  

Foodborne Listeria monocytogenes (Lm) causes serious illness and death in immunosuppressed hosts, including the elderly population. We investigated Lm susceptibility and inflammatory cytokines in geriatric mice. Young-adult and old mice were gavaged with a Lm strain Lmo-InlAm. Tissues were assayed for Lm burden and splenocytes were analyzed for Th1/Th2/Th17/Treg responses and expression of CD39 and CD73. Old Lm-infected mice lost body-weight dose-dependently, had higher Lm colonization, and showed higher inflammatory responses than Lm-infected young-adult mice. After infection, IL-17 levels increased significantly in old mice whereas IFN-γ levels were unchanged. Levels of IL-10 and Treg cells were increased in infected old mice as compared to infected young-adult mice. Age-dependent enhanced expression of CD39/CD73 was observed in purified Treg prior to infection, suggesting increased baseline adenosine production in old mice. Lm lysate-treated splenocytes from older mice produced significantly higher levels of IL-10, IL17, and IL-1β, produced less IFN-γ and IL-2, and proliferated less than splenocytes from young-adult mice. Data suggests that older mice maybe more susceptible to Lm infection due to an imbalance of Th cell responses with disproportionate and persistent anti-inflammatory responses. Lm infection enhanced differentiation of proinflammatory Th17 cells, which may also exacerbate pathological responses during listeriosis.



中文翻译:

衰老小鼠对李斯特菌病的易感性:CD39 / CD73和Th-17细胞Treg细胞表达增强的抗炎反应的作用。

食源性单核细胞增生李斯特菌(Lm)在免疫抑制的宿主(包括老年人)中引起严重的疾病和死亡。我们调查了老年小鼠的Lm敏感性和炎性细胞因子。用Lm菌株Lmo- InlA m杀死成年小鼠和成年小鼠。分析组织的Lm负荷,分析脾细胞的Th1 / Th2 / Th17 / Treg应答以及CD39和CD73的表达。与Lm感染的成年小鼠相比,受Lm感染的老小鼠体重依赖性地减轻体重,具有更高的Lm定植,并显示出更高的炎症反应。感染后,老龄小鼠的IL-17水平显着增加,而IFN-γ水平未改变。与受感染的成年小鼠相比,受感染的老小鼠中的IL-10和Treg细胞水平升高。感染前在纯化的Treg中观察到CD39 / CD73的年龄依赖性增强表达,这表明老年小鼠的基线腺苷产量增加。用Lm裂解液处理的老年小鼠脾细胞产生的IL-10,IL17和IL-1β水平明显升高,产生的IFN-γ和IL-2较少,并且比成年小鼠的脾细胞增殖少。数据表明,由于Th细胞反应与不均衡和持续的抗炎反应不平衡,老年小鼠可能更容易受到Lm感染。Lm感染增强了促炎性Th17细胞的分化,这也可能加剧李斯特菌病期间的病理反应。

更新日期:2020-01-16
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