ELF4 facilitates innate host defenses against Plasmodium by activating transcription of Pf4 and Ppbp
ELF4 facilitates innate host defenses against Plasmodium by activating transcription of Pf4 and Ppbp
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ELF4 通过激活 Pf4 和 Ppbp 的转录促进宿主对疟原虫的先天防御
DOI：
10.1074/jbc.ra118.006321
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发表时间：
2019-03
影响因子：
4.8
通讯作者：
You Fuping
中科院分区：
文献类型：
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作者：
Wang D;an;Zhang Zeming;Cui Shuang;Zhao Yingchi;Craft Samuel;Fikrig Erol;You Fuping
血小板因子4（PF 4）是血小板的抗疟原虫成分。它在巨核细胞中表达，并在疟原虫感染后从血小板中释放。天然免疫对于宿主抗疟原虫应答至关重要，其中I型干扰素起重要作用。先天免疫信号传导和抗疟原虫防御肽的产生之间是否存在串扰尚不清楚。在这里，我们证明，E74，像ETS转录因子4（ELF 4），一种I型干扰素激活剂，可以帮助保护宿主免受约氏疟原虫感染。在机械上，ELF 4与两种C-X-C趋化因子Pf 4和前血小板碱性蛋白（Ppbp）的基因的启动子结合，启动这两种基因的转录，从而增强PF 4介导的从感染的红细胞杀死寄生虫。Elf 4 −/−小鼠比WT同窝出生的小鼠更容易感染疟原虫。来自Elf 4 −/−小鼠的巨核细胞中Pf 4和Ppbp的表达水平远低于来自对照动物的表达水平，导致寄生虫血症增加。总之，我们的研究揭示了ELF 4（一种先天免疫分子）在宿主防御疟疾中的独特作用。
Platelet factor 4 (PF4) is an anti-Plasmodium component of platelets. It is expressed in megakaryocytes and released from platelets following infection with Plasmodium. Innate immunity is crucial for the host anti-Plasmodium response, in which type I interferon plays an important role. Whether there is cross-talk between innate immune signaling and the production of anti-Plasmodium defense peptides is unknown. Here we demonstrate that E74, like ETS transcription factor 4 (ELF4), a type I interferon activator, can help protect the host from Plasmodium yoelii infection. Mechanically, ELF4 binds to the promoter of genes of two C-X-C chemokines, Pf4 and pro-platelet basic protein (Ppbp), initiating the transcription of these two genes, thereby enhancing PF4-mediated killing of parasites from infected erythrocytes. Elf4−/− mice are much more susceptible to Plasmodium infection than WT littermates. The expression level of Pf4 and Ppbp in megakaryocytes from Elf4−/− mice is much lower than in those from control animals, resulting in increased parasitemia. In conclusion, our study uncovered a distinct role of ELF4, an innate immune molecule, in host defense against malaria.
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影响因子：
30.3
作者：
Love MS;Millholland MG;Mishra S;Kulkarni S;Freeman KB;Pan W;Kavash RW;Costanzo MJ;Jo H;Daly TM;Williams DR;Kowalska MA;Bergman LW;Poncz M;DeGrado WF;Sinnis P;Scott RW;Greenbaum DC
通讯作者：
Greenbaum DC
影响因子：
30.3
作者：
Srivastava, Kalyan;Cockburn, Ian A;Swaim, AnneMarie;Thompson, Laura E;Tripathi, Abhai;Fletcher, Craig A;Shirk, Erin M;Sun, Henry;Kowalska, M Anna;Fox-Talbot, Karen;Sullivan, David;Zavala, Fidel;Morrell, Craig N
通讯作者：
Morrell, Craig N
撒哈拉以南非洲疟疾研究的全球资金趋势：系统分析。
DOI：
10.1016/s2214-109x(17)30245-0
发表时间：
2017-08
期刊：
The Lancet. Global health
影响因子：
--
作者：
Head MG;Goss S;Gelister Y;Alegana V;Brown RJ;Clarke SC;Fitchett JRA;Atun R;Scott JAG;Newell ML;Padmadas SS;Tatem AJ
通讯作者：
Tatem AJ
影响因子：
3.7
作者：
Okada Y;Nobori H;Shimizu M;Watanabe M;Yonekura M;Nakai T;Kamikawa Y;Wakimura A;Funahashi N;Naruse H;Watanabe A;Yamasaki D;Fukada S;Yasui K;Matsumoto K;Sato T;Kitajima K;Nakano T;Aird WC;Doi T
通讯作者：
Doi T
影响因子：
82.9
作者：
通讯作者：
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