Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

MPYS is required for IFN response factor 3 activation and type I IFN production in the response of cultured phagocytes to bacterial second messengers cyclic-di-AMP and cyclic-di-GMP.

http://www.ncbi.nlm.nih.gov/pubmed/21813776

Cyclic-di-GMP and cyclic-di-AMP are second messengers produced by bacteria and influence bacterial cell survival, differentiation, colonization, biofilm formation, virulence, and bacteria-host interactions. In this study, we show that in both RAW264.7 macrophage cells and primary bone marrow-derived macrophages, the production of IFN-β and IL-6, but not TNF, in response to cyclic-di-AMP and cyclic-di-GMP requires MPYS (also known as STING, MITA, and TMEM173). Furthermore, expression of MPYS was required for IFN response factor 3 but not NF-κB activation in response to these bacterial metabolites. We also confirm that MPYS is required for type I IFN production by cultured macrophages infected with the intracellular pathogens Listeria monocytogenes and Francisella tularensis. However, during systemic infection with either pathogen, MPYS deficiency did not impact bacterial burdens in infected spleens. Serum IFN-β and IL-6 concentrations in the infected control and MPYS(-/-) mice were also similar at 24 h postinfection, suggesting that these pathogens stimulate MPYS-independent cytokine production during in vivo infection. Our findings indicate that bifurcating MPYS-dependent and -independent pathways mediate sensing of cytosolic bacterial infections.

Pubmed ID: 21813776 RIS Download

Mesh terms: Animals | Bacterial Infections | Cell Line | Cyclic AMP | Cyclic GMP | Cytokines | Enzyme-Linked Immunosorbent Assay | Interferon Regulatory Factor-3 | Interferon Type I | Macrophages | Membrane Proteins | Mice | Mice, Inbred C57BL | Mice, Knockout | Phagocytes | Reverse Transcriptase Polymerase Chain Reaction

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NIAID NIH HHS, Id: P01AI0222950-22
  • Agency: NIAID NIH HHS, Id: R01 AI055701
  • Agency: NIAID NIH HHS, Id: R01 AI055701-05
  • Agency: NIAID NIH HHS, Id: R01 AI065638
  • Agency: NIAID NIH HHS, Id: R01 AI065638-05
  • Agency: NIAID NIH HHS, Id: R01AI055701
  • Agency: NIAID NIH HHS, Id: R01AI062739-05
  • Agency: NIAID NIH HHS, Id: R01AI062739-05S1
  • Agency: NIAID NIH HHS, Id: R01AI062739-05S2
  • Agency: NIAID NIH HHS, Id: R01AI065638

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.