Distinctive role of efferocytosis in dendritic cell maturation and migration in sterile or infectious conditions

Immunology. 2017 Jul;151(3):304-313. doi: 10.1111/imm.12731. Epub 2017 Apr 10.

Abstract

Efferocytosis, or clearance of apoptotic cells (ACs), by dendritic cells (DCs) leads to immune response suppression and tolerance to self-antigens. However, efferocytosis of infected apoptotic cells (IACs) leads to the production of a mixed pro- and anti-inflammatory cytokine milieu. We examined the DC phenotype and ability to migrate after phagocytosis of ACs or IACs and observed higher levels of CD86 and CCR7 expression in DCs, as well as enhanced migration capacity following efferocytosis of IACs. Interestingly, higher levels of interleukin-1β, interleukin-10 and prostaglandin E2 (PGE2 ) were also produced in this context. Blockage of IAC recognition led to an impaired maturation profile and PGE2 production, which may have contributed to reduced CD86 and CCR7 expression and migration capacity. These data contribute to the understanding of how efferocytosis of sterile or infected cells may regulate the adaptive immune response, although the precise role of PGE2 in this process requires further investigation.

Keywords: CCR7; dendritic cells; efferocytosis; infected apoptotic cell; prostaglandin E2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • B7-2 Antigen / metabolism
  • Chemokine CCL19 / metabolism
  • Chemokine CCL21 / metabolism
  • Chemotaxis*
  • Coculture Techniques
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / microbiology
  • Dendritic Cells / pathology*
  • Dinoprostone / metabolism
  • Escherichia coli Infections / immunology
  • Escherichia coli Infections / metabolism
  • Escherichia coli Infections / microbiology
  • Escherichia coli Infections / pathology*
  • Female
  • Inflammation Mediators / metabolism
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Macrophages / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Phagocytosis*
  • Phenotype
  • RAW 264.7 Cells
  • Receptors, CCR7 / metabolism
  • Signal Transduction

Substances

  • B7-2 Antigen
  • Ccl19 protein, mouse
  • Ccr7 protein, mouse
  • Cd86 protein, mouse
  • Chemokine CCL19
  • Chemokine CCL21
  • Inflammation Mediators
  • Receptors, CCR7
  • Dinoprostone