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

Immunity. 2013 Sep 19;39(3):584-98. doi: 10.1016/j.immuni.2013.06.019. Epub 2013 Sep 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • Cell Differentiation
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Erythroid Cells / immunology
  • Interferon Type I / metabolism
  • Interleukin-10 / biosynthesis
  • Lymphocyte Activation
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic choriomeningitis virus / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / immunology
  • Monocytes / metabolism
  • Phagocytosis*
  • Phosphatidylserines / metabolism
  • Receptors, Cell Surface / metabolism
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Interferon Type I
  • Phosphatidylserines
  • Receptors, Cell Surface
  • phosphatidylserine receptor
  • Interleukin-10