並列タイトル等Monocyte-derived Dendritic Cells Perform Hemophagocytosis to Fine-tune Excessive Immune Responses
一般注記Since immune responses simultaneously defend and injure the host, the immune system must be finely regulated to insure the host's survival. Here, we show that when injected with high TLR ligand doses or infected with LCMV clone 13, which has a high viral turnover, inflammatory monocyte-derived dendritic cells (Mo-DCs) are induced to engulf apoptotic erythroid cells. In this process, called hemophagocytosis, extracellular ATP and phosphatidylserine (PS) serve as “find-me” and “eat-me” signals, respectively. Type I IFNs are necessary for both PS exposure on erythroid cells and the expression of PS receptors in the Mo-DCs. Importantly, hemophagocytosis is required for IL-10 production from Mo-DCs. Blocking hemophagocytosis or Mo-DC-derived IL-10 significantly increases CTL activity, tissue damage, and mortality in virus-infected hosts, suggesting that hemophagocytosis moderates immune responses to assure the host’s survival in vivo. This sheds light on the induction mechanisms and physiological relevance of hemophagocytosis in severe inflammatory and infectious diseases.
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）