title: Toll-Like Receptors 2 and 4 Cooperate in the Control of the Emerging PathogenBrucella microti.
abstract: Toll-like receptors (TLRs) recognize pathogen-derived molecules and play a critical role during the host innate and adaptive immune response.Brucellaspp. are intracellular gram-negative bacteria including several virulent species, which cause a chronic zoonotic infection in a wide range of mammalian hosts known as brucellosis. A newBrucellaspecies,Brucella microti, was recently isolated from wild rodents and found to be highly pathogenic in mice. Using this species-specific model, it was previously found that CD8+T cells are required to control this infection. In order to find out the role of TLR-mediated responses in the control of this pathogen, the course of infection ofB. microtiwas analyzed over 3 weeks in wild-type (WT) and TLR knock out (KO) mice including TLR2-/-, TLR4-/-, TLR9-/-, TLR2×4-/-and TLR2×4×9-/-. WT and single TLR2, TLR4 and TLR9 KO mice similarly control infection in liver and spleen. In contrast, bacterial clearance was delayed in TLR2×4-/-and TLR2×4×9-/-mice at 7 and 14 days post-infection. This defect correlated with impaired maturation and pro-inflammatory cytokine production inB. microti-infected dendritic cells from TLR2×4-/-and TLR2×4×9-/-mice. Finally, it was found that Tc cells from TLR2×4-/-and TLR2×4×9-/-mice showed reduced ability to inhibit growth ofB. microtiin macrophages, suggesting the involvement of TLR2 and 4 in the generation of specific Tc cells. Our findings indicate that TLR2 and TLR4 are required to controlB. microtiinfection in mice and that this effect could be related to its participation in the maturation of dendritic cells and the generation of specific CD8+Tc cells.
authors.affiliation: Cell Immunity in Cancer, Inflammation and Infection Group, Department of Biochemistry and Molecular and Cell Biology, Biomedical Research Centre of Aragon (CIBA), IIS Aragon, University of Zaragoza Zaragoza, Spain.
authors.forename: Maykel A
authors.initials: MA
authors.lastname: Arias
authors.affiliation: Cell Immunity in Cancer, Inflammation and Infection Group, Department of Biochemistry and Molecular and Cell Biology, Biomedical Research Centre of Aragon (CIBA), IIS Aragon, University of Zaragoza Zaragoza, Spain.
authors.forename: Llipsy
authors.initials: L
authors.lastname: Santiago
authors.affiliation: Cell Immunity in Cancer, Inflammation and Infection Group, Department of Biochemistry and Molecular and Cell Biology, Biomedical Research Centre of Aragon (CIBA), IIS Aragon, University of Zaragoza Zaragoza, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Costas-Ramon
authors.affiliation: Cell Immunity in Cancer, Inflammation and Infection Group, Department of Biochemistry and Molecular and Cell Biology, Biomedical Research Centre of Aragon (CIBA), IIS Aragon, University of Zaragoza Zaragoza, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Jaime-Sánchez
authors.affiliation: Max-Planck Institute for Immunobiology and Epigenetics Freiburg, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Freudenberg
authors.affiliation: Unidad de Producción y Sanidad Animal, Centro de Investigación y Tecnología Agroalimentaria, Instituto Agroalimentario de Aragón - IA2, CITA-Universidad de Zaragoza Zaragoza, Spain.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Jiménez De Bagüés
authors.affiliation: Cell Immunity in Cancer, Inflammation and Infection Group, Department of Biochemistry and Molecular and Cell Biology, Biomedical Research Centre of Aragon (CIBA), IIS Aragon, University of ZaragozaZaragoza, Spain; Nanoscience Institute of Aragon, University of ZaragozaZaragoza, Spain; Aragon I+D FoundationZaragoza, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Pardo
mesh_terms: D000818:Animals; D002002:Brucella / Q000276:immunology*; D002006:Brucellosis / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000662:veterinary*; D003713:Dendritic Cells / Q000276:immunology; D008099:Liver / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D012376:Rodent Diseases / Q000276:immunology*; D013154:Spleen / Q000382:microbiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
keywords: Brucella; dendritic cells; granzyme B; mouse model; toll-like receptors