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The overlapping host responses to bacterial cyclic dinucleotides

Ali A Abdul-Sater1, Andrzej Grajkowski, Hediye Erdjument-Bromage

  • 1Department of Microbiology & Immunology, Columbia University, New York, NY 10032, USA.

Microbes and Infection
|September 22, 2011
PubMed

Insights

Bacterial cyclic dinucleotides, like cyclic-di-GMP, trigger inflammatory responses in macrophages. These molecules activate type I Interferon (IFN-I) expression and bind to host proteins, indicating macrophages sense bacterial signals.

Area of Science:

  • Immunology
  • Microbiology
  • Molecular Biology

Background:

  • Macrophages are key immune cells that respond to bacterial infections.
  • Legionella pneumophila infection induces inflammatory mediators, including type I Interferons (IFN-Is).
  • Bacterial cyclic dinucleotides are important second messengers in microbial signaling.

Purpose of the Study:

  • To investigate if bacterial cyclic 3'-5' diguanylate (c-diGMP) activates inflammatory mediators in macrophages.
  • To explore the role of bacterial dinucleotides in macrophage inflammatory responses.
  • To identify host proteins that interact with bacterial dinucleotides.

Main Methods:

  • Macrophages were infected with L. pneumophila strains with altered c-diGMP levels.
  • Synthetic derivatives of c-diGMP and c-diAMP were used to study inflammatory responses.
  • UV crosslinking and affinity matrix fractionation were employed to identify host binding proteins.

Main Results:

  • A positive correlation was observed between c-diGMP levels and IFN-I expression in macrophages.
  • Both c-diGMP and c-diAMP activated overlapping inflammatory responses in human and murine macrophages.
  • UV crosslinking and affinity purification identified host proteins that bind to these dinucleotides.

Conclusions:

  • Mammalian macrophages can sense bacterial dinucleotides.
  • Bacterial cyclic dinucleotides like c-diGMP and c-diAMP elicit specific inflammatory responses.
  • These findings suggest a novel mechanism for host-pathogen interaction involving bacterial second messengers.

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