Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection.
Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection.
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DOI：
10.1038/s41467-018-05041-7
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发表时间：
2018-07-13
影响因子：
16.6
通讯作者：
Bucala R
中科院分区：
文献类型：
--
作者：
Baeza Garcia A;Siu E;Sun T;Exler V;Brito L;Hekele A;Otten G;Augustijn K;Janse CJ;Ulmer JB;Bernhagen J;Fikrig E;Geall A;Bucala R
疟原虫产生细胞因子巨噬细胞迁移抑制因子PMIF的直系同源物，PMIF调节宿主对疟疾的炎症反应。使用一种新的基于RNA复制子的疫苗，我们显示了PMIF免疫中和对宿主反应的影响，并观察到对肝脏和血液阶段疟原虫感染的改善控制，以及对再感染的完全保护。接种PMIF疫苗可延迟子孢子感染后的血液期开放，降低血液期感染期间Th 1相关炎症标志物TNF-α、IL-12和IFN-γ的表达，增强Tfh细胞和生发中心反应，增加抗疟原虫抗体滴度，并增强抗原经历记忆性CD 4 T细胞和肝脏驻留CD 8 T细胞的分化。通过从PMIF RNA免疫的宿主过继转移CD 8或CD 4 T细胞来概括防止再感染。寄生虫MIF抑制可能是促进对疟原虫和可能产生MIF直系同源蛋白的其他寄生虫属的免疫力的有用方法。疟原虫产生细胞因子巨噬细胞迁移抑制因子PMIF的直系同源物，PMIF调节宿主对疟疾的炎症反应。在这里，作者表明，抑制PMIF可能对管理疟疾感染有转化效益。
Plasmodium species produce an ortholog of the cytokine macrophage migration inhibitory factor, PMIF, which modulates the host inflammatory response to malaria. Using a novel RNA replicon-based vaccine, we show the impact of PMIF immunoneutralization on the host response and observed improved control of liver and blood-stage Plasmodium infection, and complete protection from re-infection. Vaccination against PMIF delayed blood-stage patency after sporozoite infection, reduced the expression of the Th1-associated inflammatory markers TNF-α, IL-12, and IFN-γ during blood-stage infection, augmented Tfh cell and germinal center responses, increased anti-Plasmodium antibody titers, and enhanced the differentiation of antigen-experienced memory CD4 T cells and liver-resident CD8 T cells. Protection from re-infection was recapitulated by the adoptive transfer of CD8 or CD4 T cells from PMIF RNA immunized hosts. Parasite MIF inhibition may be a useful approach to promote immunity to Plasmodium and potentially other parasite genera that produce MIF orthologous proteins. Plasmodium species produce an ortholog of the cytokine macrophage migration inhibitory factor, PMIF, which modulates the host inflammatory response to malaria. Here, the authors show that inhibition of PMIF may have translational benefits for managing malaria infections.
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影响因子：
30.5
作者：
Butler, Noah S.;Moebius, Jacqueline;Pewe, Lecia L.;Traore, Boubacar;Doumbo, Ogobara K.;Tygrett, Lorraine T.;Waldschmidt, Thomas J.;Crompton, Peter D.;Harty, John T.
通讯作者：
Harty, John T.
影响因子：
32.4
作者：
Nakayamada S;Kanno Y;Takahashi H;Jankovic D;Lu KT;Johnson TA;Sun HW;Vahedi G;Hakim O;Handon R;Schwartzberg PL;Hager GL;O'Shea JJ
通讯作者：
O'Shea JJ
影响因子：
4.8
作者：
Cho, Yoonsang;Jones, Brian F.;Cappello, Michael
通讯作者：
Cappello, Michael
影响因子：
4.8
作者：
Holowka, Thomas;Castilho, Tiago M.;Bucala, Richard
通讯作者：
Bucala, Richard
影响因子：
13.2
作者：
Hekele, Armin;Bertholet, Sylvie;Archer, Jacob;Gibson, Daniel G.;Palladino, Giuseppe;Brito, Luis A.;Otten, Gillis R.;Brazzoli, Michela;Buccato, Scilla;Bonci, Alessandra;Casini, Daniele;Maione, Domenico;Qi, Zhi-Qing;Gill, John E.;Caiazza, Nicky C.;Urano, Jun;Hubby, Bolyn;Gao, George F.;Shu, Yuelong;De Gregorio, Ennio;Mandl, Christian W.;Mason, Peter W.;Settembre, Ethan C.;Ulmer, Jeffrey B.;Venter, J. Craig;Dormitzer, Philip R.;Rappuoli, Rino;Geall, Andrew J.
通讯作者：
Geall, Andrew J.