Plasmodium yoelii sporozoites modulate cytokine profile and induce apoptosis in murine Kupffer cells.
Plasmodium yoelii sporozoites modulate cytokine profile and induce apoptosis in murine Kupffer cells.
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DOI：
10.1016/j.ijpara.2008.05.018
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发表时间：
2008-12
影响因子：
4
通讯作者：
Frevert U
中科院分区：
文献类型：
--
作者：
Klotz C;Frevert U
疟原虫子孢子在进入肝脏的过程中穿过库普弗细胞。子孢子接触不会引起这些肝巨噬细胞的呼吸爆发，并通过提高细胞内cAMP浓度来阻止对次要刺激的反应性氧物种的形成。在这里，我们表明，增加cAMP水平与二丁酰环腺苷一磷酸(db-cAMP)或异丁基甲基黄嘌呤(IBMX)也调节细胞因子的分泌小鼠Kupffer细胞朝着整体抗炎的方向。用脂多糖或干扰素-γ刺激暴露于约氏疟原虫子孢子的枯否细胞，可下调肿瘤坏死因子-α、IL-6和单核细胞趋化蛋白-1，上调IL-10。这种细胞因子变化的先决条件是寄生虫的生存能力和与Kupffer细胞的接触，而不是入侵。暴露于子孢子的Kupffer细胞呈TUNEL阳性，并表现出其他的凋亡死亡迹象，如膜气泡、核凝聚和碎裂，而子孢子在Kupffer细胞培养中保持完好，似乎转变为早期的红外体形式。总之，体外数据表明，疟原虫具有使库普弗细胞对促炎刺激不敏感的机制，并最终通过迫使它们进入程序性细胞死亡来消除这些巨噬细胞。
Plasmodium sporozoites traverse Kupffer cells on their way into the liver. Sporozoite contact does not elicit a respiratory burst in these hepatic macrophages and blocks the formation of reactive oxygen species in response to secondary stimuli via elevation of the intracellular cAMP concentration. Here we show that increasing the cAMP level with dibutyryl cyclic adenosine monophosphate (db-cAMP) or isobutylmethylxanthine(IBMX) also modulates cytokine secretion murine Kupffer cells towards an overall anti-inflammatory profile. Stimulation of Plasmodium yoelii sporozoite-exposed Kupffer cells with lipopolysaccharide or IFN-γ reveals down-modulation of TNF-α, IL-6 and MCP-1, and up-regulation of IL-10. Prerequisite for this shift of the cytokine profile are parasite viability and contact with Kupffer cells, but not invasion. While sporozoite-exposed Kupffer cells become TUNEL-positive and exhibit other signs of apoptotic death such as membrane blebbing, nuclear condensation and fragmentation, sporozoites remain intact and appear to transform to early exoerythrocytic forms in Kupffer cell cultures. Together, the in vitro data indicate that Plasmodium possesses mechanisms to render Kupffer cells insensitive to pro-inflammatory stimuli and eventually eliminates these macrophages by forcing them into programmed cell death.
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影响因子：
6.7
作者：
Baer K;Klotz C;Kappe SH;Schnieder T;Frevert U
通讯作者：
Frevert U
DOI：
10.1084/jem.20022100
发表时间：
2003-04-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kaiser K;Camargo N;Kappe SH
通讯作者：
Kappe SH
影响因子：
4.4
作者：
Aronoff, DM;Canetti, C;Peters-Golden, M
通讯作者：
Peters-Golden, M
影响因子：
4.4
作者：
Butcher, BA;Kim, L;Denkers, EY
通讯作者：
Denkers, EY
影响因子：
3.1
作者：
Donovan, Michael J.;Messmore, Andrew S.;McDowell, Mary Ann
通讯作者：
McDowell, Mary Ann