TY - JOUR
T1 - Monocyte-derived dendritic cells perform hemophagocytosis to fine-tune excessive immune responses
AU - Ohyagi, Hideaki
AU - Onai, Nobuyuki
AU - Sato, Taku
AU - Yotsumoto, Satoshi
AU - Liu, Jiajia
AU - Akiba, Hisaya
AU - Yagita, Hideo
AU - Atarashi, Koji
AU - Honda, Kenya
AU - Roers, Axel
AU - Müller, Werner
AU - Kurabayashi, Kazutaka
AU - Hosoi-Amaike, Mayuka
AU - Takahashi, Naoto
AU - Hirokawa, Makoto
AU - Matsushima, Kouji
AU - Sawada, Kenichi
AU - Ohteki, Toshiaki
PY - 2013/9/19
Y1 - 2013/9/19
N2 - Because immune responses simultaneously defend and injure the host, the immune system must be finely regulated to ensure the host's survival. Here, we have shown that when injected with high Toll-like receptor ligand doses or infected with lymphocytic choriomeningitis virus (LCMV) clone 13, which has a high viral turnover, inflammatory monocyte-derived dendritic cells (Mo-DCs) engulfed apoptotic erythroid cells. In this process, called hemophagocytosis, phosphatidylserine (PS) served as an "eat-me" signal. Type I interferons were necessary for both PS exposure on erythroid cells and the expression of PS receptors in the Mo-DCs. Importantly, hemophagocytosis was required for interleukin-10 (IL-10) production from Mo-DCs. Blocking hemophagocytosis or Mo-DC-derived IL-10 significantly increased cytotoxic Tcell lymphocyte activity, tissue damage, and mortality in virus-infected hosts, suggesting that hemophagocytosis moderates immune responses to ensure the host's survival invivo. This sheds light on the physiological relevance of hemophagocytosis in severe inflammatory and infectious diseases. © 2013 Elsevier Inc.
AB - Because immune responses simultaneously defend and injure the host, the immune system must be finely regulated to ensure the host's survival. Here, we have shown that when injected with high Toll-like receptor ligand doses or infected with lymphocytic choriomeningitis virus (LCMV) clone 13, which has a high viral turnover, inflammatory monocyte-derived dendritic cells (Mo-DCs) engulfed apoptotic erythroid cells. In this process, called hemophagocytosis, phosphatidylserine (PS) served as an "eat-me" signal. Type I interferons were necessary for both PS exposure on erythroid cells and the expression of PS receptors in the Mo-DCs. Importantly, hemophagocytosis was required for interleukin-10 (IL-10) production from Mo-DCs. Blocking hemophagocytosis or Mo-DC-derived IL-10 significantly increased cytotoxic Tcell lymphocyte activity, tissue damage, and mortality in virus-infected hosts, suggesting that hemophagocytosis moderates immune responses to ensure the host's survival invivo. This sheds light on the physiological relevance of hemophagocytosis in severe inflammatory and infectious diseases. © 2013 Elsevier Inc.
U2 - 10.1016/j.immuni.2013.06.019
DO - 10.1016/j.immuni.2013.06.019
M3 - Article
C2 - 24035363
SN - 1074-7613
VL - 39
SP - 584
EP - 598
JO - Immunity
JF - Immunity
IS - 3
ER -