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RECONsidering Sensing of Cyclic Dinucleotides.

Jonathan Maelfait1, Jan Rehwinkel1

  • 1Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.

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The STING pathway detects cyclic dinucleotides (cdNs) to fight viruses. Researchers discovered RECON, a mouse protein, senses bacterial cdNs, activating innate immunity independently of STING for antibacterial defense.

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Area of Science:

  • Immunology
  • Microbiology
  • Molecular Biology

Background:

  • The STING pathway is crucial for detecting cyclic dinucleotides (cdNs) and initiating antiviral responses.
  • Bacterial infections pose a significant threat, necessitating robust innate immune mechanisms for detection and clearance.

Purpose of the Study:

  • To investigate the role of the mouse oxidoreductase RECON in sensing bacterial cyclic dinucleotides.
  • To elucidate the signaling pathways involved in RECON-mediated innate immunity against bacterial pathogens.

Main Methods:

  • Utilized biochemical assays to assess RECON's binding to various bacterial cdNs.
  • Employed cell-based assays to monitor innate immune signaling activation in response to cdN stimulation.
  • Investigated the downstream signaling events modulated by RECON in a STING-independent manner.

Main Results:

  • Demonstrated that mouse RECON directly binds to and senses specific bacterial cyclic dinucleotides.
  • Showed that RECON activates innate immune signaling pathways independently of the well-characterized STING pathway.
  • Confirmed that RECON-mediated signaling contributes to an antibacterial state, enhancing host defense.

Conclusions:

  • RECON functions as a novel sensor for bacterial cyclic dinucleotides, expanding the repertoire of innate immune pattern recognition.
  • RECON-mediated STING-independent signaling represents a distinct mechanism for mounting antibacterial responses.
  • This discovery offers new insights into host-pathogen interactions and potential therapeutic targets for bacterial infections.