Strain variation in early innate cytokine induction by Plasmodium falciparum
Strain variation in early innate cytokine induction by Plasmodium falciparum
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DOI：
10.1111/j.1365-3024.2010.01225.x
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发表时间：
2010-07-01
影响因子：
2.2
通讯作者：
Rowe, J. A.
中科院分区：
文献类型：
--
作者：
Corrigan, R. A.;Rowe, J. A.
以前的研究表明，当外周血单个核细胞（PBMC）与恶性疟原虫感染的红细胞共培养时，人类供体诱导的细胞因子的大小和模式不同。恶性疟原虫菌株诱导细胞因子的能力是否不同尚未详细研究，这是一个重要的问题，因为细胞因子诱导的变化可能影响寄生虫毒力和临床疾病的模式。我们研究了对四种恶性疟原虫实验室菌株和五种田间分离株的早期炎症细胞因子反应。最初的研究表明，寄生虫菌株、寄生虫血症和PBMC供体都对促炎细胞因子应答的幅度具有显著影响（在所有情况下，IFN-γ、GM-CSF、IL-1 β、TNF-α、IL-6，P < 0，中心点005）。然而，我们注意到，最高诱导寄生虫菌株始终比其他菌株更快地达到鞭毛破裂。当考虑到树突破裂的时间时，寄生虫菌株在其细胞因子诱导方面不再有差异（P = 0，中心点383），尽管供体效应仍然显著（P < 0，中心点001）。这些数据不支持恶性疟原虫株在诱导PBMC的早期先天性细胞因子应答方面不同的假设，而是与保守的寄生虫产物如疟原虫色素或GPI锚是寄生虫衍生的细胞因子诱导刺激物的建议一致。
P>Previous work has shown that human donors vary in the magnitude and pattern of cytokines induced when peripheral blood mononuclear cells (PBMCs) are co-cultured with Plasmodium falciparum-infected erythrocytes. Whether P. falciparum strains vary in their ability to induce cytokines has not been studied in detail and is an important question, because variation in cytokine induction could affect parasite virulence and patterns of clinical disease. We investigated the early inflammatory cytokine response to four P. falciparum laboratory strains and five field isolates. Initial studies showed that parasite strain, parasitaemia and PBMC donor all had significant effects on the magnitude of pro-inflammatory cytokine responses (IFN-gamma, GM-CSF, IL-1 beta, TNF-alpha, IL-6, P < 0 center dot 005 in all cases). However, we noticed that the most highly inducing parasite strain consistently reached schizont rupture more rapidly than the other strains. When timing of schizont rupture was taken into account, parasite strains no longer differed in their cytokine induction (P = 0 center dot 383), although donor effects remained significant (P < 0 center dot 001). These data do not support the hypothesis that P. falciparum strains vary in induction of early innate cytokine responses from PBMCs, and instead are consistent with the suggestion that conserved parasite products such as haemozoin or GPI-anchors are the parasite-derived stimuli for cytokine induction.