Fraser Deborah A, Bohlson Suzanne S, Jasinskiene Nijole, Rawal Nenoo, Palmarini Gail, Ruiz Sol, Rochford Rosemary, Tenner Andrea J
Department of Molecular Biology, University of California, Irvine, 92697, USA.
J Leukoc Biol. 2006 Jul;80(1):107-16. doi: 10.1189/jlb.1105683. Epub 2006 Apr 14.
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 deficiency 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)-1alpha and IL-1beta, 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.
最近人们认识到，固有免疫反应作为对感染的强大的第一反应，在决定随后的适应性免疫反应的性质方面具有重大影响。C1q、甘露糖结合凝集素（MBL）以及防御性胶原蛋白家族的其他成员都是模式识别分子，能够在体外和体内增强对病原体、细胞碎片和凋亡细胞的吞噬作用。缺乏C1q的人类不可避免地会患上狼疮样自身免疫性疾病，对C1q基因敲除小鼠的研究表明，其在凋亡细胞清除方面存在缺陷，且有自身免疫反应倾向。此处呈现的数据表明，在吞噬作用增强的条件下，C1q和MBL在mRNA和蛋白质水平上调节细胞因子的产生。具体而言，这些固有免疫系统的识别分子向人外周血单个核细胞传递信号，导致脂多糖诱导的促炎细胞因子白细胞介素（IL）-1α和IL-1β受到抑制，而细胞因子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。这些数据支持了这样一种假说，即防御性胶原蛋白介导的对促炎反应的抑制可能是在凋亡细胞清除过程中避免自身免疫的一个重要步骤。
