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標題: A Comparative Study on Bacterial Invasion and Effects on Survival, Nitric Oxide Responses and Proinflammatory Cytokine Secretion of Raw 264.7 Macrophages Infected by Different Antibiotic-Resistant Characteristics of Salmonella Isolates
不同抗藥特性之沙門氏菌株感染小鼠巨噬細胞株Raw 264.7後之入侵及影響細胞生存、一氧化氮反應與前發炎細胞激素分泌之比較研究
作者: 陳琬婷
Wan-Ting Chen
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摘要: Salmonella is an intracellular pathogen in macrophages. This characteristic can lead the organism to more likely escape from immune clearance. Systematic infection, caused by multidrug-resistant (MDR) Salmonella, is usually associated with increased morbidity in humans and increased mortality in animals relative to non-MDR strains, and may result in difficulties during clinical treatment. It is still unclear whether MDR isolates are with higher survival in macrophages and induce less proinflammatory cytokines. This study was conducted to understand bacterial invasion and effects on survival, nitric oxide (NO) responses and proinflammatory cytokine secretion of Raw 264.7 macrophages infected by different antibiotic-resistant characteristics of Salmonella isolates. The main results indicated that nalidixic acid resistant, ciprofloxacin resistant, gryA/parC mutant and MDR strains were associated with higher invasiveness than nalidixic acid susceptible, ciprofloxacin susceptible, gryA/parC non-mutant and non-MDR strains, respectively. Macrophages after infected by ciprofloxacin susceptible and non-MDR strains were dying more rapidly than by the ciprofloxacin resistant and MDR strains during the early stage of infection (0.5 to 2 hrs), and very few cells infected by non-MDR strains could survive after 24 hrs. Lower levels of proinflammatory cytokines TNF-α and IL-6 were observed in ciprofloxacin resistant and in MDR strains. Our findings suggested that MDR isolates have higher long-term survival ability in macrophages. Moreover, macrophages infected with MDR strains secreting less proinflammatory cytokines of TNF-α and IL-6 could be less effective to clear extracellular bacteria and increase bacterial invasion.
沙門氏菌是能夠感染並於巨噬細胞內生存的胞內病原,這樣的特性使得沙門氏菌能有利於躲避免疫細胞的攻擊。目前已知多重抗藥性 (multi-drug resistant;MDR) 沙門氏菌能引起系統性的疾病,人類若受到多重抗藥性沙門氏菌感染後會增加罹病率,在動物方面若是受到多重抗藥性沙門氏菌感染則會增加死亡率,臨床上治療多重抗藥性沙門氏菌也更為困難。目前還不清楚多重抗藥性沙門氏菌菌株在感染巨噬細胞後,巨噬細胞是否具有較高的存活率、或是巨噬細胞的前發炎激素表現量是否較低。因此本研究目的想進一步了解,沙門氏菌感染巨噬細胞株後,在細菌入侵的能力、感染後巨噬細胞株的存活率、巨噬細胞株一氧化氮反應與前發炎細胞激素分泌方面,這些現象是否與感染不同抗藥特性之菌株而有差異。本研究結果發現,具nalidixic acid抗藥性、具ciprofloxacin抗藥性、gryA/parC突變或多重抗藥性菌株入侵能力皆分別高於nalidixic acid不具抗藥性、ciprofloxacin不具抗藥性、gryA/parC 未突變或非多重抗藥性菌株。感染初期0.5~2小時間,ciprofloxacin不具抗藥性或非多重抗藥性菌株感染後的巨噬細胞株相較於經ciprofloxacin具抗藥性或多重抗藥性菌株感染的巨噬細胞株而言,細菌入侵的數量多但死亡速度較快,並在24小時後觀察到受多重抗藥性菌株感染的巨噬細胞株有顯著較高的存活率 (p < 0.05)。經ciprofloxacin具抗藥性或多重抗藥性菌株感染後的巨噬細胞株,其前發炎性細胞激素TNF-α和IL-6表現量低於經ciprofloxacin不具抗藥性或非多重抗藥性菌株感染的巨噬細胞株 (p < 0.05)。本研究結果表示,多重抗藥性菌株可能在巨噬細胞株中更具有長期生存的優勢。此外,感染多重抗藥性菌株的巨噬細胞株所分泌的前發炎性細胞激素TNF-α和IL-6較少,引起初期清除胞外細菌的能力較弱,因此可能增加了抗藥性菌入侵巨噬細胞株的能力。
文章公開時間: 2017-07-10
Appears in Collections:微生物暨公共衛生學研究所



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