title: STING/MPYS mediates host defense against Listeria monocytogenes infection by regulating Ly6C(hi) monocyte migration.
abstract: 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(<tm1Camb>)), 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.
authors: Integrated Department of Immunology, University of Colorado Denver School of Medicine and National Jewish Health, Denver, CO 80206, USA. jinl@mail.amc.edu
authors: Lei
authors: L
authors: Jin
authors: Andrew
authors: A
authors: Getahun
authors: Heather M
authors: HM
authors: Knowles
authors: Jennifer
authors: J
authors: Mogan
authors: Linda J
authors: LJ
authors: Akerlund
authors: Thomas A
authors: TA
authors: Packard
authors: Anne-Laure
authors: AL
authors: Perraud
authors: John C
authors: JC
authors: Cambier
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D008088:Listeriosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008099:Liver / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008565:Membrane Proteins / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D000099197:STING Protein
chemical_list: D000950:Antigens, Ly; D008565:Membrane Proteins; C494192:Ly-6C antigen, mouse; C530855:Sting1 protein, mouse; D000099197:STING Protein
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