Susceptibility to Plasmodium liver stage infection is altered by hepatocyte polyploidy.
Susceptibility to Plasmodium liver stage infection is altered by hepatocyte polyploidy.
复制标题
DOI：
10.1111/cmi.12282
复制
发表时间：
2014-05
影响因子：
3.4
通讯作者：
Kappe SH
中科院分区：
文献类型：
--
作者：
Austin LS;Kaushansky A;Kappe SH
疟原虫寄生虫感染哺乳动物宿主的肝细胞，并在其中经历专性肝阶段发育。对于肝脏感染重要的特定宿主细胞属性在很大程度上仍然未知。在感染的肝细胞中，几种宿主信号传导途径受到干扰，其中一些在肝细胞多倍体的产生中是重要的。为了测试肝脏感染中多倍体的功能后果，我们在体外和体内用啮齿动物疟原虫约氏疟原虫感染肝细胞，并通过流式细胞术检查感染和未感染肝细胞的倍性。在这两种肝癌细胞系和小鼠肝脏中，感染细胞群中多倍体细胞的比例高于未感染细胞群。当通过比较每个倍性子集内疟原虫感染的程度来重新分析数据时，我们发现感染率在更高的多倍体细胞中升高，而在二倍体细胞中较低。此外，我们发现，寄生虫的宿主细胞的高倍性的偏好是保守的啮齿类动物疟疾物种和人类疟疾寄生虫恶性疟原虫。这种寄生虫对高倍性宿主细胞的偏好不能用肝细胞大小或DNA复制的差异来解释。我们得出结论，疟原虫优先感染和多倍体肝细胞的发展。
Plasmodium parasites infect hepatocytes of their mammalian hosts and within undergo obligate liver stage development. The specific host cell attributes that are important for liver infection remain largely unknown. Several host signaling pathways are perturbed in infected hepatocytes, some of which are important in the generation of hepatocyte polyploidy. To test the functional consequence of polyploidy in liver infection, we infected hepatocytes with the rodent malaria parasite Plasmodium yoelii both in vitro and in vivo and examined the ploidy of infected and uninfected hepatocytes by flow cytometry. In both hepatoma cell lines and in the mouse liver, the fraction of polyploid cells was higher in the infected cell population than in the uninfected cell population. When the data were reanalyzed by comparing the extent of Plasmodium infection within each ploidy subset, we found that infection rates were elevated in more highly polyploid cells and lower in diploid cells. Furthermore, we found that the parasite’s preference for host cells with high ploidy is conserved among rodent malaria species and the human malaria parasite Plasmodium falciparum. This parasite preference for host cells of high ploidy cannot be explained by differences in hepatocyte size or DNA replication. We conclude that Plasmodium preferentially infects and develops in polyploid hepatocytes.
登录
查看更多内容
影响因子：
1.7
作者：
Basiji, David A.;Ortyn, William E.;Morrissey, Philip
通讯作者：
Morrissey, Philip
影响因子：
4.7
作者：
MADRA, S;STYLES, J;SMITH, AG
通讯作者：
SMITH, AG
影响因子：
8.8
作者：
Kaushansky A;Ye AS;Austin LS;Mikolajczak SA;Vaughan AM;Camargo N;Metzger PG;Douglass AN;MacBeath G;Kappe SH
通讯作者：
Kappe SH
影响因子：
4.3
作者：
Celton-Morizur, Severine;Merlen, Gregory;Desdouets, Chantal
通讯作者：
Desdouets, Chantal
影响因子：
4
作者：
Margall-Ducos, Germain;Celton-Morizur, Severine;Desdouets, Chantal
通讯作者：
Desdouets, Chantal