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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

Open access
Jin, Lei, Hill, Krista K, Filak, Holly, Mogan, Jennifer, Knowles, Heather, Zhang, Bicheng, Perraud, Anne-Laure, Cambier, John C, Lenz, Laurel L·2011·The Journal of Immunology

Abstract

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.

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Metadata

Authors
Jin, L., Hill, K. K., Filak, H., Mogan, J., Knowles, H., Zhang, B., Perraud, A.-L., Cambier, J. C., & Lenz, L. L.
Venue
The Journal of Immunology
Published
2011-09-01
Volume
187
Issue
5
Pages
2595-2601
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W2161901483
Cited by
288
References
4
FWCI
7.24
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: 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. https://app.cochat.ai/papers/10.4049/jimmunol.1100088
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Jin, L., Hill, K. K., Filak, H., Mogan, J., Knowles, H., Zhang, B., Perraud, A.-L., Cambier, J. C., & Lenz, L. L. (2011). 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. The Journal of Immunology. https://doi.org/10.4049/jimmunol.1100088

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