A transient resistance to blood-stage malaria in interferon-γ-deficient mice through impaired production of the host cells preferred by malaria parasites.
A transient resistance to blood-stage malaria in interferon-γ-deficient mice through impaired production of the host cells preferred by malaria parasites.
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DOI：
10.3389/fmicb.2015.00600
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发表时间：
2015
影响因子：
5.2
通讯作者：
Hisaeda H
中科院分区：
文献类型：
--
作者：
Okada H;Suzue K;Imai T;Taniguchi T;Shimokawa C;Onishi R;Hirata J;Hisaeda H
IFN-γ在血液期疟疾中起病理和保护作用。其病理作用之一是通过抑制红细胞生成而导致贫血。在此，为了评估IFN-γ介导的红细胞生成改变对疟疾感染过程的影响，用两种啮齿动物疟原虫约氏疟原虫株17 XL（PyL）和17 XNL（PyNL）感染IFN-γ缺陷（GKO）小鼠，其宿主细胞范围不同。无论基因型如何，所有感染PyL的小鼠（其可以侵入任何红细胞）均出现高寄生虫血症并迅速死亡。虽然PyNL在野生型（WT）小鼠中引起短暂的非致死性感染，但一些GKO小鼠无法控制感染并死亡。然而，GKO小鼠对感染的早期阶段具有抵抗力，与WT小鼠相比，寄生虫血症的增加受损。GKO小鼠中的这种抗性与具有比WT小鼠显著更少的网织红细胞相关，网织红细胞是PyNL寄生虫的优选宿主细胞。与感染早期GKO小鼠的网织红细胞数量相比，后期这些细胞的数量显著增加，这与这些小鼠无法控制感染相吻合。我们发现PyNL寄生虫的生长与网织红细胞的量相关。因此，缺乏IFN-γ的小鼠中网织红细胞数量减少似乎是导致寄生虫生长受限的原因。值得注意的是，当给小鼠注射外源性IFN-γ时，GKO小鼠中的这些差异至少部分逆转。此外，在GKO小鼠中通过苯肼处理人工诱导溶血性贫血和增加网织红细胞完全消除了早期感染期间的较低寄生虫血症和抗性。这些结果表明，IFN-γ可能通过增加网织红细胞的量（可能是通过增强红细胞生成）促进PyNL寄生虫的早期生长。
IFN-γ plays both pathological and protective roles during blood-stage malaria. One of its pathological roles is its contribution to anemia by suppressing erythropoiesis. Here, to evaluate the effects of IFN-γ-mediated alterations in erythropoiesis on the course of malaria infection, mice deficient in IFN-γ (GKO) were infected with two strains of the rodent malaria parasite Plasmodium yoelii, 17XL (PyL) and 17XNL (PyNL), whose host cell ranges differ. Regardless of genotype, all mice infected with PyL, which can invade any erythrocyte, developed high parasitemia and died quickly. Although PyNL caused a transient non-lethal infection in wild-type (WT) mice, some GKO mice were unable to control the infection and died. However, GKO mice were resistant to the early phase of infection, showing an impaired increase in parasitemia compared with WT mice. This resistance in the GKO mice was associated with having significantly fewer reticulocytes, which are the preferred host cells for PyNL parasites, than the WT mice. Compared with the amount of reticulocytes in GKO mice during the early stages of infection, there was a significant increase in the amount of these cells at later stages, which coincided with the inability of these mice to control the infection. We found that the growth of PyNL parasites correlated with the amount of reticulocytes. Thus, the reduced number of reticulocytes in mice lacking IFN-γ appears to be responsible for the limited parasite growth. Notably, these differences in GKO mice were at least partially reversed when the mice were injected with exogenous IFN-γ. Additionally, an artificial induction of hemolytic anemia and an increase in reticulocytes by phenylhydrazine treatment in GKO mice completely abolished the lower parasitemia and resistance during early phase infection. These results suggest that IFN-γ may contribute to the early growth of PyNL parasites by increasing the amount of reticulocytes, presumably by enhancing erythropoiesis.
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影响因子：
4.6
作者：
Imai T;Ishida H;Suzue K;Hirai M;Taniguchi T;Okada H;Suzuki T;Shimokawa C;Hisaeda H
通讯作者：
Hisaeda H
IFN-γ和γδT细胞在保护性疟疾的保护性免疫中的作用。
影响因子：
7.3
作者：
Inoue S;Niikura M;Mineo S;Kobayashi F
通讯作者：
Kobayashi F
影响因子：
2.2
作者：
Favre, N;Ryffel, B;Rudin, W
通讯作者：
Rudin, W
影响因子：
16.6
作者：
Clark MA;Goheen MM;Fulford A;Prentice AM;Elnagheeb MA;Patel J;Fisher N;Taylor SM;Kasthuri RS;Cerami C
通讯作者：
Cerami C
影响因子：
4
作者：
de Back DZ;Kostova EB;van Kraaij M;van den Berg TK;van Bruggen R
通讯作者：
van Bruggen R