title: TRIL is involved in cytokine production in the brain following Escherichia coli infection.
abstract: TLR4 interactor with leucine-rich repeats (TRIL) is a brain-enriched accessory protein that is important in TLR3 and TLR4 signaling. In this study, we generated Tril(-/-) mice and examined TLR responses in vitro and in vivo. We found a role for TRIL in both TLR4 and TLR3 signaling in mixed glial cells, consistent with the high level of expression of TRIL in these cells. We also found that TRIL is a modulator of the innate immune response to LPS challenge and Escherichia coli infection in vivo. Tril(-/-) mice produce lower levels of multiple proinflammatory cytokines and chemokines specifically within the brain after E. coli and LPS challenge. Collectively, these data uncover TRIL as a mediator of innate immune responses within the brain, where it enhances neuronal cytokine responses to infection.
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland;
authors.forename: Paulina
authors.initials: P
authors.lastname: Wochal
authors.affiliation: Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605;
authors.forename: Vijay A K
authors.initials: VA
authors.lastname: Rathinam
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland;
authors.forename: Aisling
authors.initials: A
authors.lastname: Dunne
authors.affiliation: Inflammation and Immunology Research Unit, Pfizer, Cambridge, MA 02140; and.
authors.forename: Thaddeus
authors.initials: T
authors.lastname: Carlson
authors.affiliation: Global Biotherapeutic Technologies, Pfizer, Andover, MA 01810.
authors.forename: Wen
authors.initials: W
authors.lastname: Kuang
authors.affiliation: Inflammation and Immunology Research Unit, Pfizer, Cambridge, MA 02140; and.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Seidl
authors.affiliation: Inflammation and Immunology Research Unit, Pfizer, Cambridge, MA 02140; and.
authors.forename: J Perry
authors.initials: JP
authors.lastname: Hall
authors.affiliation: Inflammation and Immunology Research Unit, Pfizer, Cambridge, MA 02140; and.
authors.forename: Lih-Ling
authors.initials: LL
authors.lastname: Lin
authors.affiliation: Inflammation and Immunology Research Unit, Pfizer, Cambridge, MA 02140; and.
authors.forename: Mary
authors.initials: M
authors.lastname: Collins
authors.affiliation: Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605;
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Schattgen
authors.affiliation: Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605;
authors.forename: Christopher R
authors.initials: CR
authors.lastname: MacKay
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland;
authors.forename: Caio T
authors.initials: CT
authors.lastname: Fagundes
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605;
authors.forename: Susan
authors.initials: S
authors.lastname: Carpenter
authors.affiliation: Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605;
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Fitzgerald
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; laoneill@tcd.ie.
authors.forename: Luke A J
authors.initials: LA
authors.lastname: O'Neill
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis; D004926:Escherichia coli / Q000276:immunology; D004927:Escherichia coli Infections / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009457:Neuroglia / Q000276:immunology; D011070:Poly I-C / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology; D051200:Toll-Like Receptor 8 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D002352:Carrier Proteins; C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C519703:TLR3 protein, mouse; C552579:TLR8 protein, mouse; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; C477038:Tlr7 protein, mouse; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; C543715:Tril protein, mouse; D014409:Tumor Necrosis Factor-alpha; D011070:Poly I-C