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Detection of a vita-PAMP STINGs cells into reticulophagy

Julien Moretti1,2, J Magarian Blander1,2,3,4,5

  • 1a The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine , Cornell University , New York , NY USA.

Autophagy
|May 22, 2018
PubMed

Insights

Phagocytes detect live bacteria using vita-PAMPs like cyclic-di-adenosine monophosphate (c-di-AMP). This triggers endoplasmic reticulum stress and reticulophagy, crucial for innate immunity and cell balance.

Area of Science:

  • Immunology
  • Cell Biology
  • Microbiology

Background:

  • Phagocytes distinguish live from dead bacteria using vita-PAMPs.
  • Gram-positive bacteria utilize cyclic-di-adenosine monophosphate (c-di-AMP) as a vita-PAMP.
  • TMEM173/STING is an innate sensor for c-di-AMP.

Purpose of the Study:

  • To elucidate the role of TMEM173/STING in response to live Gram-positive bacteria.
  • To investigate the interplay between ER stress, MTOR, reticulophagy, and type I IFN signaling.
  • To understand how these pathways maintain phagocyte homeostasis and innate immunity.

Main Methods:

  • Detection of c-di-AMP by TMEM173/STING in phagocytes.
  • Analysis of endoplasmic reticulum (ER) stress responses.
  • Assessment of MTOR inactivation and reticulophagy.
  • Characterization of type I IFN production.

Main Results:

  • Internalized live Gram-positive bacteria trigger TMEM173/STING sensing of c-di-AMP.
  • This activates ER stress, MTOR inactivation, and reticulophagy.
  • Reticulophagy facilitates TMEM173/STING relocalization to phagophores, promoting signaling.
  • ER-stress induced autophagy resolves stress and prevents apoptosis, while reticulophagy orchestrates type I IFN response.

Conclusions:

  • Reticulophagy is a key process linking ER stress and innate immune signaling via TMEM173/STING.
  • The described pathway is essential for phagocyte homeostasis and effective innate immunity against live bacteria.
  • TMEM173/STING-dependent reticulophagy is critical for orchestrating type I IFN responses.
Keywords:
ER stressER-phagyGram-positive bacteriaMTORSTINGautophagyc-di-AMPcell-autonomous innate immunitytype-I interferonvita-PAMP

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