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Induction of type I IFN is a physiological immune reaction to apoptotic cell-derived membrane microparticles

Martin Schiller1, Marijo Parcina, Petra Heyder

  • 1Division of Rheumatology, Department of Internal Medicine V, University Hospital Heidelberg, D-69120 Heidelberg, Germany. martin.schiller@med.uni-heidelberg.de

Journal of Immunology (Baltimore, Md. : 1950)
|July 13, 2012
PubMed

Insights

Membrane microparticles (MMP) from apoptotic cells activate plasmacytoid dendritic cells (pDC) to secrete IFN-α. This response is mediated by DNA within MMP binding to TLR9, a key finding in immune regulation.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Membrane microparticles (MMP) from apoptotic cells modulate immune responses.
  • Plasmacytoid dendritic cells (pDC) are crucial regulators of immune homeostasis.
  • The interaction between MMP and pDC in initiating anti-inflammatory signals is not fully understood.

Purpose of the Study:

  • To investigate the effects of apoptotic cell-derived MMP on human pDC.
  • To identify the mechanisms by which MMP influence pDC function.
  • To determine the role of specific molecular components and receptors in this interaction.

Main Methods:

  • Isolation and treatment of human pDC with MMP from apoptotic cells.
  • Measurement of IFN-α secretion by pDC.
  • Inhibition studies using cytochalasin D, chloroquine, and oligodeoxynucleotides.
  • Analysis of MMP-DNA and MMP-RNA stimulatory activity.
  • Assessment of FcγRIIA (CD32A) involvement.

Main Results:

  • Apoptotic cell-derived MMP trigger significant IFN-α secretion from human pDC.
  • The stimulatory effect is primarily mediated by DNA within MMP (MMP-DNA), with higher activity than MMP-RNA or other DNA sources.
  • TLR9 was identified as the receptor for MMP-DNA, as confirmed by inhibitory studies.
  • In healthy subjects, MMP-induced IFN-α secretion by pDC is independent of FcγRIIA (CD32A).

Conclusions:

  • The induction of IFN-α by MMP in pDC is a physiological process.
  • MMP-DNA interaction with TLR9 is a key pathway for pDC activation.
  • Further research is needed to clarify whether this pDC activation promotes inflammation or tolerance during apoptotic cell clearance.

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