Neutrophil paralysis in Plasmodium vivax malaria.
Neutrophil paralysis in Plasmodium vivax malaria.
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DOI：
10.1371/journal.pntd.0001710
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发表时间：
2012
影响因子：
3.8
通讯作者：
Gazzinelli RT
中科院分区：
文献类型：
--
作者：
Leoratti FM;Trevelin SC;Cunha FQ;Rocha BC;Costa PA;Gravina HD;Tada MS;Pereira DB;Golenbock DT;Antonelli LR;Gazzinelli RT
间日疟原虫对先天免疫应答的激活导致效应细胞的激活和促炎细胞因子的过度产生，这可能导致有害作用。在这里，我们研究了中性粒细胞的激活和功能在疟疾急性发作。在入院时（第0天）和用氯喹和伯氨喹治疗后30-45天从间日疟原虫感染的患者收集血液样品。通过流式细胞仪微珠试验测量高度纯化的单核细胞和中性粒细胞产生的活化标志物的表达和细胞因子水平。吞噬活性，超氧化物的产生，趋化性和G蛋白偶联受体（GRK 2）的存在下，疟疾患者的中性粒细胞也进行了评价。间日疟原虫感染患者的单核细胞和中性粒细胞均高度活化。虽然单核细胞被发现是响应TLR配体的细胞因子的主要来源，但中性粒细胞显示出增强的吞噬活性和超氧化物产生。有趣的是，来自疟疾患者的中性粒细胞表达高水平的GRK 2，低水平的CXCR 2，并显示出对IL-8（CXCL 8）的趋化性受损。来自疟疾患者的活化的中性粒细胞是促炎细胞因子的不良来源，并且显示出降低的趋化活性，这表明疟疾期间对继发性细菌感染的易感性增强的可能机制。 间日疟原虫是造成世界上大约60-80%的疟疾病例的原因，并且在拉丁美洲和亚洲的发展中国家造成严重的社会和经济不稳定。间日疟原虫疟疾的发病机制是宿主衍生的炎症介质的结果。因此，更好地了解间日疟原虫疟疾期间诱导全身炎症的机制对于临床管理和预防严重疾病至关重要。先天性免疫受体识别疟原虫并启动介导抗感染的广谱宿主防御机制。然而，先天免疫反应是经典的“双刃剑”，临床疟疾与高水平的循环促炎细胞因子相关。我们的研究结果表明，单核细胞和中性粒细胞在疟疾期间高度活化。急性期单核细胞产生高水平的IL-1β、IL-6和TNF-α。另一方面，中性粒细胞是细胞因子的不良来源，但显示出增强的吞噬活性和超氧化物产生。出乎意料的是，我们注意到中性粒细胞对IL-8（CXCL 8）梯度的趋化性受损。我们认为中性粒细胞麻痹是疟疾患者对细菌感染易感性增强的部分原因。
The activation of innate immune responses by Plasmodium vivax results in activation of effector cells and an excessive production of pro-inflammatory cytokines that may culminate in deleterious effects. Here, we examined the activation and function of neutrophils during acute episodes of malaria. Blood samples were collected from P. vivax-infected patients at admission (day 0) and 30–45 days after treatment with chloroquine and primaquine. Expression of activation markers and cytokine levels produced by highly purified monocytes and neutrophils were measured by the Cytometric Bead Assay. Phagocytic activity, superoxide production, chemotaxis and the presence of G protein-coupled receptor (GRK2) were also evaluated in neutrophils from malaria patients. Both monocytes and neutrophils from P. vivax-infected patients were highly activated. While monocytes were found to be the main source of cytokines in response to TLR ligands, neutrophils showed enhanced phagocytic activity and superoxide production. Interestingly, neutrophils from the malaria patients expressed high levels of GRK2, low levels of CXCR2, and displayed impaired chemotaxis towards IL-8 (CXCL8). Activated neutrophils from malaria patients are a poor source of pro-inflammatory cytokines and display reduced chemotactic activity, suggesting a possible mechanism for an enhanced susceptibility to secondary bacterial infection during malaria. Plasmodium vivax is responsible for approximately 60–80% of the malaria cases in the world, and contributes to significant social and economic instability in the developing countries of Latin America and Asia. The pathogenesis of P. vivax malaria is a consequence of host derived inflammatory mediators. Hence, a better understanding of the mechanisms involved in induction of systemic inflammation during P. vivax malaria is critical for the clinical management and prevention of severe disease. The innate immune receptors recognize Plasmodium sp. and initiate a broad spectrum of host defense mechanisms that mediate resistance to infection. However, the innate immune response is the classic “two-edged sword”, and clinical malaria is associated with high levels of circulating pro-inflammatory cytokines. Our findings show that both monocytes and neutrophils are highly activated during malaria. Monocytes produced high levels of IL-1β, IL-6 and TNF-α during acute malaria. On the other hand, neutrophils were a poor source of cytokines, but displayed an enhanced phagocytic activity and superoxide production. Unexpectedly, we noticed an impaired chemotaxis of neutrophils towards an IL-8 (CXCL8) gradient. We proposed that neutrophil paralysis is in part responsible for the enhanced susceptibility to bacterial infection observed in malaria patients.
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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
Toll样受体9介导疟疾色素血液唑素的先天免疫激活。
DOI：
10.1084/jem.20041836
发表时间：
2005-01-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Coban C;Ishii KJ;Kawai T;Hemmi H;Sato S;Uematsu S;Yamamoto M;Takeuchi O;Itagaki S;Kumar N;Horii T;Akira S
通讯作者：
Akira S
以核酸感应 Toll 样受体为治疗靶点可预防实验性脑疟疾
DOI：
10.1073/pnas.1015406108
发表时间：
2011-03-01
影响因子：
11.1
作者：
Franklin, Bernardo S.;Ishizaka, Sally T.;Gazzinelli, Ricardo T.
通讯作者：
Gazzinelli, Ricardo T.
DOI：
10.1073/pnas.0809742106
发表时间：
2009-04-07
影响因子：
11.1
作者：
Franklin, Bernardo S.;Parroche, Peggy;Gazzinelli, Ricardo T.
通讯作者：
Gazzinelli, Ricardo T.
影响因子：
82.9
作者：
Fan, J;Malik, AB
通讯作者：
Malik, AB