title: Monocyte-derived dendritic cells perform hemophagocytosis to fine-tune excessive immune responses.
abstract: 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 T cell lymphocyte activity, tissue damage, and mortality in virus-infected hosts, suggesting that hemophagocytosis moderates immune responses to ensure the host's survival in vivo. This sheds light on the physiological relevance of hemophagocytosis in severe inflammatory and infectious diseases.
authors.affiliation: Department of Hematology, Nephrology and Rheumatology, Akita University Graduate School of Medicine, Akita 010-8543, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ohyagi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Onai
authors.forename: Taku
authors.initials: T
authors.lastname: Sato
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yotsumoto
authors.forename: Jiajia
authors.initials: J
authors.lastname: Liu
authors.forename: Hisaya
authors.initials: H
authors.lastname: Akiba
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Koji
authors.initials: K
authors.lastname: Atarashi
authors.forename: Kenya
authors.initials: K
authors.lastname: Honda
authors.forename: Axel
authors.initials: A
authors.lastname: Roers
authors.forename: Werner
authors.initials: W
authors.lastname: Müller
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Kurabayashi
authors.forename: Mayuka
authors.initials: M
authors.lastname: Hosoi-Amaike
authors.forename: Naoto
authors.initials: N
authors.lastname: Takahashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Hirokawa
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sawada
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ohteki
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D041905:Erythroid Cells / Q000276:immunology; D007370:Interferon Type I / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D007370:Interferon Type I; D010718:Phosphatidylserines; D011956:Receptors, Cell Surface; C408123:phosphatidylserine receptor; D016753:Interleukin-10