Immunological profiles associated with distinct parasitemic states in volunteers undergoing malaria challenge in Gabon.
Immunological profiles associated with distinct parasitemic states in volunteers undergoing malaria challenge in Gabon.
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在加蓬接受疟疾挑战的志愿者中与不同寄生虫状态相关的免疫学特征。
DOI：
10.1038/s41598-022-17725-8
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发表时间：
2022-08-03
影响因子：
4.6
通讯作者：
Yazdanbakhsh, Maria
中科院分区：
文献类型：
--
作者：
Manurung, Mikhael D.;de Jong, Sanne E.;Kruize, Yvonne;Mouwenda, Yoanne D.;Ongwe, Madeleine Eunice Betouke;Honkpehedji, Yabo Josiane;Zinsou, Jeannot Frezus;Dejon-Agobe, Jean Claude;Hoffman, Stephen L.;Kremsner, Peter G.;Adegnika, Ayola Akim;Fendel, Rolf;Mordmuller, Benjamin;Roestenberg, Meta;Lell, Bertrand;Yazdanbakhsh, Maria
使用冷冻保存的非减毒恶性疟原虫孢子体（PfSPZ）进行的受控人体疟疾感染（CHMI）为研究自然获得性免疫（NAI）提供了独特的机会。通过分析5名未感染过疟疾的欧洲成年人和20名终生接触疟疾的非洲成年人在接受Sanaria® PfSPZ Challenge直接静脉接种（DVI）之前、接种后5天和11天的血液样本，我们评估了与控制显微镜下和亚显微镜下寄生虫血症相关的免疫模式。所有（5/5）欧洲个体都出现了厚血涂片（TBS）所定义的寄生虫血症，但40%（8/20）的非洲个体控制住了他们的寄生虫血症，因此厚血涂片呈阴性（非洲TBS - 个体）。在非洲TBS - 个体中，我们观察到产生干扰素 - γ（IFNγ）的CD4 + T细胞的基线频率较高，在PfSPZ DVI后5天显著下降。非洲TBS - 个体代表了具有非常强且快速的血液阶段免疫或对肝脏阶段免疫的个体，他们被分为具有亚显微镜下寄生虫血症（TBS - PCR +）的个体和可能具有绝育免疫（TBS - PCR -）的个体。基线时较高频率的IFNγ + TNF + CD8 + γδ T细胞，在PfSPZ DVI后5天内下降，与那些保持TBS - PCR - 的个体相关。这些发现表明，自然获得性免疫的特征是不同细胞类型对疟原虫的控制能力不同。虽然外周血中高频率的抗原反应性IFNγ + CD4 + T细胞将血液阶段的寄生虫控制在亚显微镜水平，但与肝脏阶段免疫或快速清除血液阶段寄生虫相关的是IFNγ + TNF + CD8 + γδ T细胞。
Controlled human malaria infection (CHMI) using cryopreserved non-attenuated Plasmodium falciparum sporozoites (PfSPZ) offers a unique opportunity to investigate naturally acquired immunity (NAI). By analyzing blood samples from 5 malaria-naïve European and 20 African adults with lifelong exposure to malaria, before, 5, and 11 days after direct venous inoculation (DVI) with SanariaR PfSPZ Challenge, we assessed the immunological patterns associated with control of microscopic and submicroscopic parasitemia. All (5/5) European individuals developed parasitemia as defined by thick blood smear (TBS), but 40% (8/20) of the African individuals controlled their parasitemia, and therefore remained thick blood smear-negative (TBS− Africans). In the TBS− Africans, we observed higher baseline frequencies of CD4+ T cells producing interferon-gamma (IFNγ) that significantly decreased 5 days after PfSPZ DVI. The TBS− Africans, which represent individuals with either very strong and rapid blood-stage immunity or with immunity to liver stages, were stratified into subjects with sub-microscopic parasitemia (TBS-PCR+) or those with possibly sterilizing immunity (TBS−PCR−). Higher frequencies of IFNγ+TNF+CD8+ γδ T cells at baseline, which later decreased within five days after PfSPZ DVI, were associated with those who remained TBS−PCR−. These findings suggest that naturally acquired immunity is characterized by different cell types that show varying strengths of malaria parasite control. While the high frequencies of antigen responsive IFNγ+CD4+ T cells in peripheral blood keep the blood-stage parasites to a sub-microscopic level, it is the IFNγ+TNF+CD8+ γδ T cells that are associated with either immunity to the liver-stage, or rapid elimination of blood-stage parasites.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
RTS，S/AS01E疟疾疫苗在小儿非洲III期试验中诱导记忆和多功能T细胞反应。
影响因子：
7.3
作者：
Moncunill G;De Rosa SC;Ayestaran A;Nhabomba AJ;Mpina M;Cohen KW;Jairoce C;Rutishauser T;Campo JJ;Harezlak J;Sanz H;Díez-Padrisa N;Williams NA;Morris D;Aponte JJ;Valim C;Daubenberger C;Dobaño C;McElrath MJ
通讯作者：
McElrath MJ
影响因子：
4.3
作者：
Gaballa, Ahmed;Arruda, Lucas C. M.;Uhlin, Michael
通讯作者：
Uhlin, Michael
影响因子：
4.4
作者：
Kadivar, Mohammad;Petersson, Julia;Marsal, Jan
通讯作者：
Marsal, Jan
影响因子：
82.9
作者：
Ishizuka, Andrew S.;Lyke, Kirsten E.;Seder, Robert A.
通讯作者：
Seder, Robert A.