Monocyte-derived dendritic cells perform hemophagocytosis to fine-tune excessive immune responses

Hideaki Ohyagi, Nobuyuki Onai, Taku Sato, Satoshi Yotsumoto, Jiajia Liu, Hisaya Akiba, Hideo Yagita, Koji Atarashi, Kenya Honda, Axel Roers, Werner Müller, Kazutaka Kurabayashi, Mayuka Hosoi-Amaike, Naoto Takahashi, Makoto Hirokawa, Kouji Matsushima, Kenichi Sawada, Toshiaki Ohteki

Research output: Contribution to journalArticle

42 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)584-598
Number of pages15
JournalImmunity
Volume39
Issue number3
DOIs
Publication statusPublished - 2013 Sep 19
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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  • Cite this

    Ohyagi, H., Onai, N., Sato, T., Yotsumoto, S., Liu, J., Akiba, H., Yagita, H., Atarashi, K., Honda, K., Roers, A., Müller, W., Kurabayashi, K., Hosoi-Amaike, M., Takahashi, N., Hirokawa, M., Matsushima, K., Sawada, K., & Ohteki, T. (2013). Monocyte-derived dendritic cells perform hemophagocytosis to fine-tune excessive immune responses. Immunity, 39(3), 584-598. https://doi.org/10.1016/j.immuni.2013.06.019