Perry James A, Olver Christine S, Burnett Robert C, Avery Anne C
Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
J Immunol. 2005 May 15;174(10):5921-5. doi: 10.4049/jimmunol.174.10.5921.
An effective immune response to infection requires control of pathogen growth while minimizing inflammation-associated pathology. During malaria infection, this balance is particularly important. Murine malaria is characterized by early production of proinflammatory cytokines, which declines in the face of continuing parasitemia. The mechanism by which this occurs remains poorly understood. In this study, we investigated the role of dendritic cells (DCs) in regulating pro- and anti-inflammatory cytokine responses. As malaria infection progresses, DCs become refractory to TLR-mediated IL-12 and TNF-alpha production, while increasing their ability to produce IL-10 and retaining the capacity for activation of naive T cells. IL-12-secreting DCs from early infection stimulate an IFN-gamma-dominated T cell response, whereas IL-10-secreting DCs from later stages induce an IL-10-dominated T cell response. We suggest that phenotypic changes in DCs during Plasmodium yoelii infection represent a mechanism of controlling host inflammation while maintaining effective adaptive immunity.
对感染产生有效的免疫反应需要控制病原体的生长，同时尽量减少与炎症相关的病理变化。在疟疾感染期间，这种平衡尤为重要。鼠疟的特征是促炎细胞因子早期产生，而在持续的寄生虫血症情况下其水平会下降。这种情况发生的机制仍知之甚少。在本研究中，我们调查了树突状细胞（DCs）在调节促炎和抗炎细胞因子反应中的作用。随着疟疾感染的进展，DCs对TLR介导的IL-12和TNF-α产生变得不敏感，同时增加其产生IL-10的能力并保留激活初始T细胞的能力。早期感染时分泌IL-12的DCs刺激以IFN-γ为主导的T细胞反应，而后期分泌IL-10的DCs诱导以IL-10为主导的T细胞反应。我们认为，约氏疟原虫感染期间DCs的表型变化代表了一种在维持有效的适应性免疫的同时控制宿主炎症的机制。
