瘧原蟲是一種導(dǎo)致人類瘧疾并且使得這種疾病特別致命性的寄生蟲。在一項(xiàng)新研究中,，美國耶魯大學(xué)研究人員發(fā)現(xiàn),，它擁有一種獨(dú)特的避免遭受人體免疫系統(tǒng)破壞的能力，從而削減人體產(chǎn)生免疫力和對(duì)抗感染的能力,。2012年7月9日,，相關(guān)研究結(jié)果在線發(fā)表在PNAS期刊上。
在高傳播地區(qū),，控制瘧疾的最大問題之一就是缺乏對(duì)抗再次感染的保護(hù)性免疫,。人們認(rèn)為對(duì)抗感染的記憶T細(xì)胞形成和維持不充足是這種免疫系統(tǒng)障礙產(chǎn)生的根源。這種現(xiàn)象也使得開發(fā)出有效的抗瘧疾疫苗的努力遭受挫折,。
眾所周知,，瘧疾在被感染的個(gè)人體內(nèi)導(dǎo)致強(qiáng)烈的炎癥反應(yīng)，而這種炎癥反應(yīng)導(dǎo)致致命性的臨床并發(fā)癥：貧血和腦部疾病,。在這項(xiàng)研究中,，耶魯大學(xué)研究小組了解到瘧原蟲產(chǎn)生它們自己的人細(xì)胞因子蛋白版本，而且在瘧疾期間,，這種細(xì)胞因子促進(jìn)炎癥反應(yīng)產(chǎn)生,。他們也發(fā)現(xiàn)，這種被稱作PMIF的細(xì)胞因子使得抗瘧疾的記憶T細(xì)胞免疫反應(yīng)不能發(fā)揮作用,。
耶魯大學(xué)研究小組在小鼠體內(nèi)利用一種經(jīng)過基因改造的瘧原蟲菌株開展研究,，結(jié)果發(fā)現(xiàn)PMIF導(dǎo)致宿主T細(xì)胞形成短命的效應(yīng)細(xì)胞而不是保護(hù)性記憶細(xì)胞。這種短命的細(xì)胞在感染期間死亡,，而長壽的記憶T細(xì)胞并不能足夠地產(chǎn)生從而來對(duì)抗感染或者阻止在瘧疾流行區(qū)域重復(fù)性發(fā)生的再次感染,。
耶魯大學(xué)醫(yī)學(xué)院內(nèi)科、病理學(xué),、流行病學(xué)和公共衛(wèi)生學(xué)教授Rick Bucala博士說,，“這些發(fā)現(xiàn)表明瘧原蟲主動(dòng)地干涉免疫記憶的產(chǎn)生，而且可能解釋人瘧疾中保護(hù)性免疫反應(yīng)遭受抑制的原因,。這些知識(shí)將有助于我們開發(fā)出特異性的療法來保護(hù)抗瘧疾T細(xì)胞不會(huì)死掉和改善人體對(duì)感染產(chǎn)生的免疫反應(yīng)或者開發(fā)出相應(yīng)的疫苗,。”(生物谷：Bioon.com)
本文編譯自How malaria evades the body's immune response
doi:10.1073/pnas.1206573109
PMC:
PMID:
A Plasmodium-encoded cytokine suppresses T-cell immunity during malaria
Tiffany Suna, Thomas Holowkaa, Yan Songa, Swen Zierowb, Lin Lenga, Yibang Chenc, Huabao Xiongd, Jason Griffitha, Mehdi Nouraiee, Philip E. Thumaf, Elias Lolisb, Chris J. Janseg, Victor R. Gordeuke, Kevin Augustijng, and Richard Bucala
The inability to acquire protective immunity against Plasmodia is the chief obstacle to malaria control, and inadequate T-cell responses may facilitate persistent blood-stage infection. Malaria is characterized by a highly inflammatory cytokine milieu, and the lack of effective protection against infection suggests that memory T cells are not adequately formed or maintained. Using a genetically targeted strain of Plasmodium berghei, we observed that the Plasmodium ortholog of macrophage migration inhibitory factor enhanced inflammatory cytokine production and also induced antigen-experienced CD4 T cells to develop into short-lived effector cells rather than memory precursor cells. The short-lived effector CD4 T cells were more susceptible to Bcl-2–associated apoptosis, resulting in decreased CD4 T-cell recall responses against challenge infections. These findings indicate that Plasmodia actively interfere with the development of immunological memory and may account for the evolutionary conservation of parasite macrophage migration inhibitory factor orthologs.
