STING/MPYS mediates host defense against Listeria monocytogenes infection by regulating Ly6C(hi) monocyte migration

MPYS (also known as STING, MITA, and TMEM173) is a type I IFN stimulator that is essential for host defense against DNA virus infection and appears important in defense against certain bacteria. The in vivo significance and mechanisms by which MPYS mediates host defense against nonviral pathogens ar...

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Published inThe Journal of immunology (1950) Vol. 190; no. 6; pp. 2835 - 2843
Main Authors Jin, Lei, Getahun, Andrew, Knowles, Heather M, Mogan, Jennifer, Akerlund, Linda J, Packard, Thomas A, Perraud, Anne-Laure, Cambier, John C
Format Journal Article
LanguageEnglish
Published United States 15.03.2013
Subjects
Animals
Antigens, Ly - biosynthesis
Cell Movement - genetics
Cell Movement - immunology
Cells, Cultured
Disease Models, Animal
Host-Pathogen Interactions - genetics
Host-Pathogen Interactions - immunology
Listeriosis - genetics
Listeriosis - immunology
Listeriosis - pathology
Liver - immunology
Liver - microbiology
Liver - pathology
Membrane Proteins - deficiency
Membrane Proteins - physiology
Mice
Mice, 129 Strain
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Monocytes - immunology
Monocytes - microbiology
Monocytes - pathology
Spleen - immunology
Spleen - microbiology
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Summary:MPYS (also known as STING, MITA, and TMEM173) is a type I IFN stimulator that is essential for host defense against DNA virus infection and appears important in defense against certain bacteria. The in vivo significance and mechanisms by which MPYS mediates host defense against nonviral pathogens are unknown. Using an MPYS-deficient mouse (Tmem173()), we determined that, distinct from the IFNAR(-/-) mice, MPYS deficiency leads to increased bacterial burden in the liver upon Listeria monocytogenes infection. The increase was correlated with the diminished MCP-1 and MCP-3 chemokine production and decreased blood and liver Ly6C(hi) monocyte frequency. We further demonstrate that MPYS-deficient Ly6C(hi) monocytes are intrinsically defective in migration to the liver. Lastly, adoptive transfer of wild-type Ly6C(hi) monocyte into MPYS-deficient mice decreases their liver bacterial burden. Our findings reveal a novel in vivo function of MPYS that is distinct from its role in activating type I IFN production.
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ISSN:1550-6606
DOI:10.4049/jimmunol.1201788