CD19(+) B cells confer protection against experimental cerebral malaria in semi-immune rodent model.

CD19(+) B cells confer protection against experimental cerebral malaria in semi-immune rodent model.
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DOI:
10.1371/journal.pone.0064836
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Hirayama K
Hirayama K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bao LQ;Huy NT;Kikuchi M;Yanagi T;Senba M;Shuaibu MN;Honma K;Yui K;Hirayama K

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在非洲脑型疟流行区,成人比儿童更易感染脑型疟,这可能与获得性部分免疫或半免疫状态有关。在这里,我们开发了一个实验性脑疟疾(ECM)模型的半免疫小鼠。C57 BL/6(B6)小鼠在最后用104伯氏疟原虫ANKA攻击而不治疗之前经历一个、两个和三个周期的感染和根治性治疗(分别为1-治愈、2-治愈和3-治愈)。我们的结果显示,100%的未感染(0-治愈),67%的1-治愈,37%的2-治愈和3-治愈小鼠在攻击感染后10天内死于ECM。在受保护的3-治愈小鼠中,在攻击感染后第7天观察到血浆IL-10水平显著高于其他小鼠,而IFN-γ水平显著低于其他小鼠。3-cure小鼠IL-10阳性细胞中主要增加的淋巴细胞亚群为CD 5(-)CD 19(+)B细胞。被动转移来自3-cure小鼠的脾CD 19(+)细胞可保护未处理小鼠免受ECM影响。此外,3岁治愈小鼠在最后一次攻击感染后12个月和20个月也受到ECM的保护。总之,小鼠在三次暴露于疟疾后对ECM完全具有抵抗力。CD 19(+)B细胞是半免疫小鼠抗ECM保护机制的决定因素,可能通过调节IL-10产生致病性IFN-γ。
In African endemic area, adults are less vulnerable to cerebral malaria than children probably because of acquired partial immunity or semi-immune status. Here, we developed an experimental cerebral malaria (ECM) model for semi-immune mice. C57BL/6 (B6) mice underwent one, two and three cycles of infection and radical treatment (1-cure, 2-cure and 3-cure, respectively) before being finally challenged with 104 Plasmodium berghei ANKA without treatment. Our results showed that 100% of naïve (0-cure), 67% of 1-cure, 37% of 2-cure and none of 3-cure mice succumbed to ECM within 10 days post challenge infection. In the protected 3-cure mice, significantly higher levels of plasma IL-10 and lower levels of IFN-γ than the others on day 7 post challenge infection were observed. Major increased lymphocyte subset of IL-10 positive cells in 3-cure mice was CD5(−)CD19(+) B cells. Passive transfer of splenic CD19(+) cells from 3-cure mice protected naïve mice from ECM. Additionally, aged 3-cure mice were also protected from ECM 12 and 20 months after the last challenge infection. In conclusion, mice became completely resistant to ECM after three exposures to malaria. CD19(+) B cells are determinants in protective mechanism of semi-immune mice against ECM possibly via modulatory IL-10 for pathogenic IFN-γ production.
DOI: 10.1038/nm1499
发表时间: 2006-12-01
期刊: NATURE MEDICINE
影响因子: 82.9
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