Identification of GAPDH on the surface of Plasmodium sporozoites as a new candidate for targeting malaria liver invasion.
Identification of GAPDH on the surface of Plasmodium sporozoites as a new candidate for targeting malaria liver invasion.
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DOI：
10.1084/jem.20160059
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发表时间：
2016-09-19
期刊：
影响因子：
--
通讯作者：
Jacobs-Lorena M
中科院分区：
文献类型：
--
作者：
Cha SJ;Kim MS;Pandey A;Jacobs-Lorena M
Cha等人表明子孢子表面上的疟原虫GAPDH作为结合库普弗细胞CD 68的配体，这是一种对寄生虫肝侵入至关重要的相互作用。因此，疟原虫GAPDH是肝前疟疾疫苗的候选抗原。疟疾的传播始于受感染的蚊子将疟原虫子孢子送入皮肤。子孢子随后进入循环并通过优先穿过枯否细胞（肝窦衬里的巨噬细胞样组分）感染肝脏。通过筛选噬菌体展示文库，我们先前鉴定了一种命名为P39的肽，其结合枯否细胞表面上的CD 68并阻断子孢子穿越。在这项研究中，我们表明，P39肽是一个结构模拟的甘油醛3-磷酸脱氢酶（GAPDH）的子孢子表面和GAPDH直接与库普弗细胞表面上的CD 68相互作用。重要的是，抗P39抗体显著抑制子孢子肝侵入，而不与哺乳动物GAPDH交叉反应。因此，疟原虫特异性GAPDH表位可能为肝前疫苗的开发提供新的抗原。
Cha et al. show that Plasmodium GAPDH on the sporozoite surface acts as a ligand for binding Kupffer cell CD68, an interaction that is critical for parasite liver invasion. Thus, Plasmodium GAPDH is a candidate antigen for a prehepatic malaria vaccine. Malaria transmission begins when an infected mosquito delivers Plasmodium sporozoites into the skin. The sporozoite subsequently enters the circulation and infects the liver by preferentially traversing Kupffer cells, a macrophage-like component of the liver sinusoidal lining. By screening a phage display library, we previously identified a peptide designated P39 that binds to CD68 on the surface of Kupffer cells and blocks sporozoite traversal. In this study, we show that the P39 peptide is a structural mimic of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) on the sporozoite surface and that GAPDH directly interacts with CD68 on the Kupffer cell surface. Importantly, an anti-P39 antibody significantly inhibits sporozoite liver invasion without cross-reacting with mammalian GAPDH. Therefore, Plasmodium-specific GAPDH epitopes may provide novel antigens for the development of a prehepatic vaccine.
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影响因子：
64.8
作者：
Kim, Min-Sik;Pinto, Sneha M.;Getnet, Derese;Nirujogi, Raja Sekhar;Manda, Srikanth S.;Chaerkady, Raghothama;Madugundu, Anil K.;Kelkar, Dhanashree S.;Isserlin, Ruth;Jain, Shobhit;Thomas, Joji K.;Muthusamy, Babylakshmi;Leal-Rojas, Pamela;Kumar, Praveen;Sahasrabuddhe, Nandini A.;Balakrishnan, Lavanya;Advani, Jayshree;George, Bijesh;Renuse, Santosh;Selvan, Lakshmi Dhevi N.;Patil, Arun H.;Nanjappa, Vishalakshi;Radhakrishnan, Aneesha;Prasad, Samarjeet;Subbannayya, Tejaswini;Raju, Rajesh;Kumar, Manish;Sreenivasamurthy, Sreelakshmi K.;Marimuthu, Arivusudar;Sathe, Gajanan J.;Chavan, Sandip;Datta, Keshava K.;Subbannayya, Yashwanth;Sahu, Apeksha;Yelamanchi, Soujanya D.;Jayaram, Savita;Rajagopalan, Pavithra;Sharma, Jyoti;Murthy, Krishna R.;Syed, Nazia;Goel, Renu;Khan, Aafaque A.;Ahmad, Sartaj;Dey, Gourav;Mudgal, Keshav;Chatterjee, Aditi;Huang, Tai-Chung;Zhong, Jun;Wu, Xinyan;Shaw, Patrick G.;Freed, Donald;Zahari, Muhammad S.;Mukherjee, Kanchan K.;Shankar, Subramanian;Mahadevan, Anita;Lam, Henry;Mitchell, Christopher J.;Shankar, Susarla Krishna;Satishchandra, Parthasarathy;Schroeder, John T.;Sirdeshmukh, Ravi;Maitra, Anirban;Leach, Steven D.;Drake, Charles G.;Halushka, Marc K.;Prasad, T. S. Keshava;Hruban, Ralph H.;Kerr, Candace L.;Bader, Gary D.;Iacobuzio-Donahue, Christine A.;Gowda, Harsha;Pandey, Akhilesh
通讯作者：
Pandey, Akhilesh
影响因子：
6.7
作者：
Ghosh, Anil K.;Devenport, Martin;Jethwaney, Deepa;Kalume, Dario E.;Pandey, Akhilesh;Anderson, Vernon E.;Sultan, Ali A.;Kumar, Nirbhay;Jacobs-Lorena, Marcelo
通讯作者：
Jacobs-Lorena, Marcelo
影响因子：
2.4
作者：
MEIS, JFGM;VERHAVE, JP;MEUWISSEN, JHET
通讯作者：
MEUWISSEN, JHET
影响因子：
6.4
作者：
Jin H;Agarwal S;Agarwal S;Pancholi V
通讯作者：
Pancholi V
影响因子：
7
作者：
Lindner, Scott E.;Swearingen, Kristian E.;Kappe, Stefan H. I.
通讯作者：
Kappe, Stefan H. I.