Deletion of a malaria invasion gene reduces death and anemia, in model hosts.

Deletion of a malaria invasion gene reduces death and anemia, in model hosts.
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DOI:
10.1371/journal.pone.0025477
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Haldar K
Haldar K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Gómez ND;Safeukui I;Adelani AA;Tewari R;Reddy JK;Rao S;Holder A;Buffet P;Mohandas N;Haldar K

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疟疾寄生虫在多种哺乳动物宿主中诱导复杂的细胞和临床表型,包括贫血、脑型疟疾和死亡。宿主基因和寄生虫“毒素”与疟疾疾病有关,但寄生虫基因的作用仍有待充分确定。在这里,我们评估疾病的BALB/c小鼠和Wistar大鼠感染的啮齿类疟原虫伯氏疟原虫裂殖子表面蛋白(MSP)7基因敲除。MSP 7不是感染所必需的,但在恶性疟原虫中,它使红细胞侵入增强20%。在体内,与野生型相比,伯氏疟原虫Δ msp 7突变体与死亡的消除和循环寄生虫血症峰值从3%降低至2%相关。Δ msp 7突变体还与贫血减少和脾脏中卵泡大小适度增加相关。总之,这些数据表明,删除一个单一的寄生虫入侵配体调节血液阶段的疾病,如死亡和贫血。这项工作是第一次评估严重疾病中所有疟原虫物种中存在的基因的贡献。
Malaria parasites induce complex cellular and clinical phenotypes, including anemia, cerebral malaria and death in a wide range of mammalian hosts. Host genes and parasite ‘toxins’ have been implicated in malarial disease, but the contribution of parasite genes remains to be fully defined. Here we assess disease in BALB/c mice and Wistar rats infected by the rodent malaria parasite Plasmodium berghei with a gene knock out for merozoite surface protein (MSP) 7. MSP7 is not essential for infection but in P. falciparum, it enhances erythrocyte invasion by 20%. In vivo, as compared to wild type, the P. berghei Δmsp7 mutant is associated with an abrogation of death and a decrease from 3% to 2% in peak, circulating parasitemia. The Δmsp7 mutant is also associated with less anemia and modest increase in the size of follicles in the spleen. Together these data show that deletion of a single parasite invasion ligand modulates blood stage disease, as measured by death and anemia. This work is the first to assess the contribution of a gene present in all plasmodial species in severe disease.
DOI: 10.1038/nature07327
发表时间: 2008-10-09
期刊: NATURE
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发表时间: 2005-11-15
期刊: BLOOD
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发表时间: 2006-01-01
影响因子: 1.5
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DOI: 10.1182/blood-2005-08-3460
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影响因子: 20.3
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通讯作者: Schofield, L