C1q and MBL, components of the innate immune system, influence monocyte cytokine expression
C1q and MBL, components of the innate immune system, influence monocyte cytokine expression
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DOI：
10.1189/jlb.1105683
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发表时间：
2006-07-01
影响因子：
5.5
通讯作者：
Tenner, Andrea J.
中科院分区：
文献类型：
--
作者：
Fraser, Deborah A.;Bohlson, Suzanne S.;Tenner, Andrea J.
最近已经认识到，先天免疫应答，即对感染的强有力的第一应答，在决定随后的适应性免疫应答的性质方面具有显著影响。C1 q、甘露糖结合凝集素（MBL）和防御胶原蛋白家族的其他成员是模式识别分子，能够增强体外和体内对病原体、细胞碎片和凋亡细胞的吞噬作用。缺乏C1 q的人类不可避免地会发展成狼疮样自身免疫性疾病，并且在C1 q敲除小鼠中的研究表明，在清除凋亡细胞方面存在缺陷，具有自身免疫反应的倾向。本文提供的数据表明，在吞噬作用增强的条件下，C1 q和MBL在mRNA和蛋白质水平上调节细胞因子的产生。具体而言，先天免疫系统的这些识别分子向人外周血单核细胞提供信号，导致脂多糖诱导的促炎细胞因子白介素（IL）-1 α和IL-1 β的抑制，以及细胞因子IL-10、IL-1受体拮抗剂、单核细胞趋化蛋白-1和IL-6的分泌增加。这些数据支持的假设，防御胶原介导的抑制促炎反应可能是一个重要的步骤，在避免自身免疫过程中清除凋亡细胞。
It has recently been recognized that the innate immune response, the powerful first response to infection, has significant influence in determining the nature of the subsequent adaptive immune response. C1q, mannose-binding lectin (MBL), and other members of the defense collagen family of proteins are pattern recognition molecules, able to enhance the phagocytosis of pathogens, cellular debris, and apoptotic cells in vitro and in vivo. Humans deficient in C1q inevitably develop a lupus-like autoimmune disorder, and studies in C1q knockout mice demonstrate a deficieney in the clearance of apoptotic cells with a propensity for autoimmune responses. The data presented here show that under conditions in which phagocytosis is enhanced, C1q and MBL modulate cytokine production at the mRNA and protein levels. Specifically, these recognition molecules of the innate immune system contribute signals to human peripheral blood mononuclear cells, leading to the suppression of lipopolysaccharide-induced proinflammatory cytokines, interleukin (IL)-1 alpha and IL-1 beta, and an increase in the secretion of cytokines IL-10, IL-1 receptor antagonist, monocyte chemoattractant protein-1, and IL-6. These data support the hypothesis that defense collagen-mediated suppression of a proinflammatory response may be an important step in the avoidance of autoimmunity during the clearance of apoptotic cells.