Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
Parasite Immunol. 2010 Jul;32(7):512-27. doi: 10.1111/j.1365-3024.2010.01225.x.
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 < 0.005 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 = 0.383), although donor effects remained significant (P < 0.001). 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.
先前的研究表明，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，人类供体在细胞因子的诱导幅度和模式上存在差异。尚未详细研究恶性疟原虫株在诱导细胞因子的能力上是否存在差异，这是一个重要的问题，因为细胞因子诱导的差异可能会影响寄生虫的毒力和临床疾病的模式。我们研究了四种恶性疟原虫实验室株和五种现场分离株对早期炎症细胞因子的反应。初步研究表明，寄生虫株、寄生虫血症和 PBMC 供体均对促炎细胞因子反应的幅度有显著影响（IFN-γ、GM-CSF、IL-1β、TNF-α、IL-6，所有情况下 P<0.005）。然而，我们注意到，诱导性最强的寄生虫株始终比其他株更早达到裂殖体破裂。当考虑到裂殖体破裂的时间时，寄生虫株在细胞因子诱导方面不再存在差异（P=0.383），尽管供体效应仍然显著（P<0.001）。这些数据不支持恶性疟原虫株在诱导 PBMC 早期先天细胞因子反应方面存在差异的假设，而是与这样的观点一致，即保守的寄生虫产物，如疟原血红素或 GPI 锚定物，是诱导细胞因子的寄生虫源性刺激物。
