A systematic analysis of the human immune response to Plasmodium vivax.
A systematic analysis of the human immune response to Plasmodium vivax.
复制标题
DOI：
10.1172/jci152463
复制
发表时间：
2023-10-16
影响因子：
15.9
通讯作者：
Spence, Philip J.
中科院分区：
文献类型：
--
作者：
Bach, Florian A.;Sandoval, Diana Munoz;Mazurczyk, Michalina;Themistocleous, Yrene;Rawlinson, Thomas A.;Harding, Adam C.;Kemp, Alison;Silk, Sarah E.;Barrett, Jordan R.;Edwards, Nick J.;Ivens, Alasdair;Rayner, Julian C.;Minassian, Angela M.;Napolitani, Giorgio;Draper, Simon J.;Spence, Philip J.
间日疟原虫的生物学特性与恶性疟原虫显著不同；这如何影响对感染的免疫反应仍不清楚。为了解决这一不足，我们给志愿者接种了间日疟原虫的克隆场分离株，并跟踪了他们在感染和康复过程中的反应。参与者被静脉注射血液期寄生虫，并通过定量PCR实时跟踪感染动态。全血样本用于高维蛋白质分析、RNA测序和飞行时间细胞术，并通过线性回归量化宿主对间日疟原虫反应的时间变化。然后使用来自先前控制的人类疟疾感染研究的类似数据集与恶性疟原虫进行比较分析。间日疟原虫迅速引起I型炎症反应，这与临床疟疾的显著特征相吻合。这种急性时相反应与恶性疟原虫引起的反应有显著重叠，但显著升高(在RNA和蛋白质水平)，导致发热发生率增加。相反，感染恶性疟原虫的志愿者T细胞活化和终末分化显著增加。不同的CD4+T细胞被发现主导这种适应性反应，表型分析揭示了通常与细胞毒性和自身炎症性疾病相关的意想不到的特征。间日疟原虫触发全身干扰素信号的增加(参见恶性疟原虫)，这可能是其热原阈值降低的原因。相比之下，恶性疟原虫推动T细胞活化的能力远远超过间日疟原虫，这可能在一定程度上解释了为什么恶性疟疾更容易导致严重疾病。临床试验.gov NCT03797989。欧盟的地平线2020研究和创新计划、惠康信托基金和皇家学会。
The biology of Plasmodium vivax is markedly different from that of P. falciparum; how this shapes the immune response to infection remains unclear. To address this shortfall, we inoculated human volunteers with a clonal field isolate of P. vivax and tracked their response through infection and convalescence. Participants were injected intravenously with blood-stage parasites and infection dynamics were tracked in real time by quantitative PCR. Whole blood samples were used for high dimensional protein analysis, RNA sequencing, and cytometry by time of flight, and temporal changes in the host response to P. vivax were quantified by linear regression. Comparative analyses with P. falciparum were then undertaken using analogous data sets derived from prior controlled human malaria infection studies. P. vivax rapidly induced a type I inflammatory response that coincided with hallmark features of clinical malaria. This acute-phase response shared remarkable overlap with that induced by P. falciparum but was significantly elevated (at RNA and protein levels), leading to an increased incidence of pyrexia. In contrast, T cell activation and terminal differentiation were significantly increased in volunteers infected with P. falciparum. Heterogeneous CD4+ T cells were found to dominate this adaptive response and phenotypic analysis revealed unexpected features normally associated with cytotoxicity and autoinflammatory disease. P. vivax triggers increased systemic interferon signaling (cf P. falciparum), which likely explains its reduced pyrogenic threshold. In contrast, P. falciparum drives T cell activation far in excess of P. vivax, which may partially explain why falciparum malaria more frequently causes severe disease. ClinicalTrials.gov NCT03797989. The European Union’s Horizon 2020 Research and Innovation programme, the Wellcome Trust, and the Royal Society.
登录
查看更多内容
DOI：
10.1086/510756
发表时间：
2007-02-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Anstey NM;Handojo T;Pain MC;Kenangalem E;Tjitra E;Price RN;Maguire GP
通讯作者：
Maguire GP
HCV患者血液单核细胞（PBMC）抑制核糖体蛋白合成和蛋白质翻译因子。
影响因子：
7.4
作者：
Gupta R;Kim S;Taylor MW
通讯作者：
Taylor MW
致死性小儿疟疾淋巴结和脾切片中淋巴细胞亚群的特征。
DOI：
10.3390/pathogens11080851
发表时间：
2022-07-28
期刊：
Pathogens (Basel, Switzerland)
影响因子：
--
作者：
通讯作者：
--
DOI：
10.4269/ajtmh.2009.09-0194
发表时间：
2009-11
期刊：
The American journal of tropical medicine and hygiene
影响因子：
--
作者：
Herrera S;Fernández O;Manzano MR;Murrain B;Vergara J;Blanco P;Palacios R;Vélez JD;Epstein JE;Chen-Mok M;Reed ZH;Arévalo-Herrera M
通讯作者：
Arévalo-Herrera M
DOI：
10.4269/ajtmh.20-0491
发表时间：
2020-11
期刊：
The American journal of tropical medicine and hygiene
影响因子：
--
作者：
Odedra A;Webb L;Marquart L;Britton LJ;Chalon S;Moehrle JJ;Anstey NM;William T;Grigg MJ;Lalloo DG;Barber BE;McCarthy JS
通讯作者：
McCarthy JS