More time to kill: A longer liver stage increases T cell-mediated protection against pre-erythrocytic malaria.
More time to kill: A longer liver stage increases T cell-mediated protection against pre-erythrocytic malaria.
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更多的杀戮时间：更长的肝脏阶段增加了T细胞介导的对前红细胞疟疾的保护。
DOI：
10.1016/j.isci.2023.108489
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发表时间：
2023-12-15
期刊：
影响因子：
5.8
通讯作者：
Murphy, Sean C.
中科院分区：
文献类型：
--
作者：
Yadav, Naveen;Parthiban, Chaitra;Billman, Zachary P.;Stone, Brad C.;Watson, Felicia N.;Zhou, Kevin;Olsen, Tayla M.;Talavera, Irene Cruz;Seilie, Annette Mariko;Kalata, Anya C.;Matsubara, Jokichi;Shears, Melanie J.;Reynolds, Rebekah A.;Murphy, Sean C.
肝期（LS）：啮齿动物的疟原虫在2-2.5天内成熟，而人类则在5-6天内成熟。疟原虫特异性CD8+ T细胞扩增在这些不同的时间跨度中有所不同。为了模拟人疟原虫感染CD8+ T细胞的动力学，建立了一种双剂量刺激小鼠模型，达到4-5天的LS抗原暴露。在该模型中，小鼠接种了一种无保护性的、低剂量的迟发性基因减毒孢子体来启动T细胞活化，然后在2-3天后再次接种野生型孢子体。部分防范传统攻击的疫苗完全防范两剂攻击。在攻毒期间，双剂量攻毒小鼠肝脏中的CD8+ T细胞频率增加，而传统攻毒小鼠的肝脏中CD8+ T细胞频率没有增加，进一步表明该模型更好地再现了恶性疟原虫LS期间人体内CD8+ T细胞扩增的动力学。疫苗开发和抗原发现工作可以通过使用两剂攻击策略得到帮助。更长时间的疟疾肝期暴露凸显了CD8+ T细胞在保护中的作用小鼠双剂量攻击模型提供了更长的疟原虫肝期暴露疫苗诱导免疫可针对更长时间的肝期双剂量攻击免疫得到改善；肝脏病学;生物化学
Liver stage (LS) Plasmodia mature in 2–2.5 days in rodents compared to 5–6 days in humans. Plasmodium-specific CD8+ T cell expansion differs across these varied timespans. To mimic the kinetics of CD8+ T cells of human Plasmodium infection, a two-dose challenge mouse model that achieved 4–5 days of LS antigen exposure was developed. In this model, mice were inoculated with a non-protective, low dose of late-arresting, genetically attenuated sporozoites to initiate T cell activation and then re-inoculated 2–3 days later with wild-type sporozoites. Vaccines that partially protected against traditional challenge completely protected against two-dose challenge. During the challenge period, CD8+ T cell frequencies increased in the livers of two-dose challenged mice but not in traditionally challenged mice, further suggesting that this model better recapitulates kinetics of CD8+ T cell expansion in humans during the P. falciparum LS. Vaccine development and antigen discovery efforts may be aided by using the two-dose challenge strategy. Longer malaria liver stage exposure highlights the role of CD8+ T cells in protection A two-dose challenge model in mice provides longer Plasmodium liver stage exposure Vaccine-induced immunity is improved against the longer liver stage two-dose challenge Immunology; Hepatology; Biochemistry
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DOI：
10.4291/wjgp.v5.i2.107
发表时间：
2014-05-15
期刊：
World journal of gastrointestinal pathophysiology
影响因子：
--
作者：
Hammerich, Linda;Tacke, Frank
通讯作者：
Tacke, Frank
影响因子：
3.1
作者：
Medica, DL;Sinnis, P
通讯作者：
Sinnis, P
影响因子：
3.1
作者：
Liehl, Peter;Meireles, Patrcia;Prudencio, Miguel
通讯作者：
Prudencio, Miguel
影响因子：
16.6
作者：
Minkah, Nana K.;Wilder, Brandon K.;Kappe, Stefan H., I
通讯作者：
Kappe, Stefan H., I
影响因子：
8.8
作者：
Lefebvre MN;Surette FA;Anthony SM;Vijay R;Jensen IJ;Pewe LL;Hancox LS;Van Braeckel-Budimir N;van de Wall S;Urban SL;Mix MR;Kurup SP;Badovinac VP;Butler NS;Harty JT
通讯作者：
Harty JT