title: Toll-Like Receptor 2 Mediates In Vivo Pro- and Anti-inflammatory Effects of Mycobacterium Tuberculosis and Modulates Autoimmune Encephalomyelitis.
abstract: Mycobacteria display pro- and anti-inflammatory effects in human and experimental pathology. We show here that both effects are mediated by Toll-like receptor 2 (Tlr2), by exploiting a previously characterized Tlr2 variant (Met82Ile). Tlr2 82ile promoted self-specific proinflammatory polarization as well as expansion of ag-specific FoxP3(+) Tregs, while Tlr2 82met impairs the expansion of Tregs and reduces the production of IFN-γ and IL-17 proinflammatory cytokines. Preferential dimerization with Tlr1 or Tlr6 could not explain these differences. In silico, we showed that Tlr2 variant Met82Ile modified the binding pocket for peptidoglycans and participated directly to a putative binding pocket for sugars and cadherins. The distinct pro- and anti-inflammatory actions impacted severity, extent of remission, and distribution of the lesions within the central nervous system of experimental autoimmune encephalomyelitis. Thus, Tlr2 has a janus function in vivo as mediator of the role of bacterial products in balancing pro- and anti-inflammatory immune responses.
authors.affiliation: Laboratory of Immunology, Institute of General Pathology, Università Cattolica del Sacro Cuore , Rome , Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Piermattei
authors.affiliation: Laboratory of Immunology, Institute of General Pathology, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Public Health and Infectious Diseases, University "La Sapienza", Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Migliara
authors.affiliation: Laboratory of Immunology, Institute of General Pathology, Università Cattolica del Sacro Cuore, Rome, Italy; Institute of Rheumatology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Di Sante
authors.affiliation: Molecular Medicine and Immunology Laboratory, Genopolis Consortium, University of "Milano Bicocca" , Milan , Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Foti
authors.affiliation: Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences , Sofia , Bulgaria.
authors.forename: Soren Bohos
authors.initials: SB
authors.lastname: Hayrabedyan
authors.affiliation: Molecular Medicine and Immunology Laboratory, Genopolis Consortium, University of "Milano Bicocca" , Milan , Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Papagna
authors.affiliation: Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore , Rome , Italy.
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Geloso
authors.affiliation: Institute of General Pathology, Università Cattolica del Sacro Cuore , Rome , Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Corbi
authors.affiliation: Laboratory of Immunology, Institute of General Pathology, Università Cattolica del Sacro Cuore , Rome , Italy.
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Valentini
authors.affiliation: Institute of General Pathology, Università Cattolica del Sacro Cuore , Rome , Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sgambato
authors.affiliation: Institute of Microbiology, Università Cattolica del Sacro Cuore , Rome , Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Delogu
authors.affiliation: Section of General Pathology, Department of Medicine, University of Verona , Verona , Italy.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Constantin
authors.affiliation: Laboratory of Immunology, Institute of General Pathology, Università Cattolica del Sacro Cuore , Rome , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ria
keywords: EAE/MS; Foxp3; TLR2; host–pathogen interactions; inflammation