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Dendritic Cells Induce Immunity and Long-Lasting Protection against Blood-Stage Malaria despite an In Vitro Parasite-Induced Maturation Defect

机译:树突状细胞尽管有体外寄生虫诱导的成熟缺陷,但仍能抵抗免疫力并长期防御血站期疟疾。

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Dendritic cells (DC) suffer a maturation defect following interaction with erythrocytes infected with malaria parasites and become unable to induce protective malaria liver-stage immunity. Here we show that, by contrast, maturation-arrested DC in vitro are capable of the successful induction of antigen-specific gamma interferon (IFN-γ) and interleukin 4 (IL-4) T-cell responses, antibody responses, and potent protection against lethal blood-stage malaria challenge in vivo. Similar results were found with DC pulsed with intact parasitized Plasmodium yoelii or Plasmodium chabaudi erythrocytes. Cross-strain protection was also induced. High levels of protection (80 to 100%) against lethal challenge were evident from 10 days after a single immunization and maintained up to 120 days. Interestingly, correlation studies versus blood-stage protection at different time points suggest that the immune effector mechanisms associated with protection could change over time. Antibody-independent, T-cell- and IL-12-associated protection was observed early after immunization, followed by antibody and IL-4-associated, IFN-γ-independent protection in long-term studies. These results indicate that DC, even when clearly susceptible to parasite-induced maturation defect effects in vitro, can be central to the induction of protection against blood-stage malaria in vivo.
机译:树突状细胞(DC)与感染了疟原虫的红细胞相互作用后会出现成熟缺陷,并无法诱导保护性疟疾肝阶段免疫。相比之下,在这里我们显示,体外抑制成熟的DC能够成功诱导抗原特异性γ干扰素(IFN-γ)和白介素4(IL-4)T细胞应答,抗体应答以及有效的保护在体内对抗致命的血液阶段疟疾的挑战。用完整的寄生化的约氏疟原虫 chabaudi疟原虫红细胞脉冲直流电也发现了相似的结果。还诱导了交叉应变保护。从单次免疫后的10天开始,就可以对致死性攻击进行高水平的保护(80%至100%),并保持长达120天。有趣的是,在不同时间点对血液保护的相关性研究表明,与保护相关的免疫效应机制可能随时间而改变。在长期免疫研究中,在免疫后早期观察到与抗体无关的T细胞和IL-12相关的保护,然后与抗体和IL-4相关的IFN-γ独立的保护。这些结果表明,DC,即使在体外明显易受寄生虫诱导的成熟缺陷影响,也可能在体内诱导针对血液阶段疟疾的保护中发挥重要作用。

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