title: Engagement of Toll-like receptor 2 in mouse macrophages infected with Mycobacterium avium induces non-oxidative and TNF-independent anti-mycobacterial activity.
abstract: Toll-like receptor (TLR) 2 plays an important role in the immune response to mycobacterial infections, being required for optimal immunity against certain virulent Mycobacterium avium strains. Here we analyzed the role of TLR2 in the intra-macrophagic growth of M. avium, using macrophages from TLR2-deficient mice. We found that the engagement of TLR2/TLR6 and/or TLR2/TLR1 receptors induced bacteriostasis of M. avium inside bone marrow-derived macrophages in a MyD88-dependent way. Additionally, lipoproteins from the cell envelope of M. avium with a molecular mass of 20-25 kDa triggered this TLR2 pathway, leading to a decrease in the growth of the mycobacteria. Although TLR2 engagement induced the production of TNF, this cytokine as well as nitric oxide and superoxide molecules were not necessary for TLR2-mediated bacteriostasis. Finally, TLR ligation did not induce the expression of the 47-kDa guanosine triphosphatase (LRG-47) but it promoted an increased maturation of the phagosome with regards to acquisition of LAMP1. Our data show that triggering TLR2 inhibited M. avium growth by an as-yet-unknown mechanism that may involve increased phagosome maturation.
authors.affiliation: Laboratory of Microbiology and Immunology of Infection, IBMC-Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal.
authors.forename: M Salomé
authors.initials: MS
authors.lastname: Gomes
authors.forename: Sofia
authors.initials: S
authors.lastname: Sousa Fernandes
authors.forename: João V
authors.initials: JV
authors.lastname: Cordeiro
authors.forename: Sandro
authors.initials: S
authors.lastname: Silva Gomes
authors.forename: André
authors.initials: A
authors.lastname: Vieira
authors.forename: Rui
authors.initials: R
authors.lastname: Appelberg
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009162:Mycobacterium avium / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D013481:Superoxides / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000502:physiology*; D051216:Toll-Like Receptor 6 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; C495369:Tlr6 protein, mouse; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009569:Nitric Oxide