title: Internalization and TLR-dependent type I interferon production by monocytes in response to Toxoplasma gondii.
abstract: The classic anti-viral cytokine interferon (IFN)-β can be induced during parasitic infection, but relatively little is know about the cell types and signaling pathways involved. Here we show that inflammatory monocytes (IMs), but not neutrophils, produce IFN-β in response to T. gondii infection. This difference correlated with the mode of parasite entry into host cells, with phagocytic uptake predominating in IMs and active invasion predominating in neutrophils. We also show that expression of IFN-β requires phagocytic uptake of the parasite by IMs, and signaling through Toll-like receptors (TLRs) and MyD88. Finally, we show that IMs are major producers of IFN-β in mesenteric lymph nodes following in vivo oral infection of mice, and mice lacking the receptor for type I IFN-1 show higher parasite loads and reduced survival. Our data reveal a TLR and internalization-dependent pathway in IMs for IFN-β induction to a non-viral pathogen.
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, CA, USA.
authors.forename: Seong-Ji
authors.initials: SJ
authors.lastname: Han
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, CA, USA.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Melichar
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, CA, USA.
authors.forename: Janine L
authors.initials: JL
authors.lastname: Coombes
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, CA, USA.
authors.forename: Shiao Wei
authors.initials: SW
authors.lastname: Chan
authors.affiliation: Department of Medicine (Infectious Disease) and Department of Neurology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Anita A
authors.initials: AA
authors.lastname: Koshy
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Boothroyd
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, CA, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Barton
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, CA, USA.
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Robey
mesh_terms: D000818:Animals; D007113:Immunity, Innate; D016899:Interferon-beta / Q000096:biosynthesis*; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*; D014122:Toxoplasma / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000469:parasitology
chemical_list: D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors; D016899:Interferon-beta