Document Detail

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.
MedLine Citation:
PMID:  21813776     Owner:  NLM     Status:  MEDLINE    
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.
Lei Jin; Krista K Hill; Holly Filak; Jennifer Mogan; Heather Knowles; Bicheng Zhang; Anne-Laure Perraud; John C Cambier; Laurel L Lenz
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-08-03
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  187     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-08-22     Completed Date:  2011-10-19     Revised Date:  2014-09-10    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2595-601     Citation Subset:  AIM; IM    
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MeSH Terms
Bacterial Infections / immunology,  metabolism
Cell Line
Cyclic AMP / immunology*,  metabolism
Cyclic GMP / analogs & derivatives*,  immunology,  metabolism
Cytokines / biosynthesis,  immunology
Enzyme-Linked Immunosorbent Assay
Interferon Regulatory Factor-3 / immunology*,  metabolism
Interferon Type I / biosynthesis,  immunology*
Macrophages / immunology*,  metabolism
Membrane Proteins / immunology*,  metabolism
Mice, Inbred C57BL
Mice, Knockout
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
P01AI0222950-22/AI/NIAID NIH HHS; R01 AI055701/AI/NIAID NIH HHS; R01 AI055701-05/AI/NIAID NIH HHS; R01 AI065638/AI/NIAID NIH HHS; R01 AI065638-05/AI/NIAID NIH HHS; R01AI055701/AI/NIAID NIH HHS; R01AI062739-05/AI/NIAID NIH HHS; R01AI062739-05S1/AI/NIAID NIH HHS; R01AI062739-05S2/AI/NIAID NIH HHS; R01AI065638/AI/NIAID NIH HHS
Reg. No./Substance:
0/Cytokines; 0/Interferon Regulatory Factor-3; 0/Interferon Type I; 0/Irf3 protein, mouse; 0/MPYS protein, mouse; 0/Membrane Proteins; 61093-23-0/bis(3',5')-cyclic diguanylic acid; E0399OZS9N/Cyclic AMP; H2D2X058MU/Cyclic GMP

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