title: Mycobacterium tuberculosis lipids regulate cytokines, TLR-2/4 and MHC class II expression in human macrophages.
abstract: The interaction of macrophages with Mycobacterium tuberculosis through Toll-like receptors is critical in defining the cytokine profile that may or may not control disease progression. Cell-wall lipids are the main pathogen-associated molecular ligands of mycobacteria, in this paper, we analysed how lipid fractions of three different strains of the M. tuberculosis complex (genotypes Canetti, Beijing and H37Rv) affected the innate immunity by regulating TNF-alpha and IL-10 secretion, TLR2, TLR4, and MHC class II expression of human monocyte-derived macrophages. Of note, lipid fractions from the Beijing genotype (hypervirulent phenotype) preferentially induced macrophages to secrete high amounts of TNF-alpha and IL-10, but downregulated TLR2, TLR4 and MHC class II expression. In contrast, lipids from M. tuberculosis Canetti induced lower amounts of TNF-alpha and IL-10, upregulated TLR2 and TLR4 without modifying MHC class II expression. These results indicate that the virulent mycobacterial genotype Beijing expresses lipids that negatively modified cytokine, TLR and MHC class II expression. These findings may help to unravel the complex mechanisms used by virulent mycobacteria to evade and subvert the immune response.
authors.affiliation: Departamento de Infectología, Hospital Infantil de México, Secretaría de Salud, México D.F., Mexico.
authors.forename: Luz María
authors.initials: LM
authors.lastname: Rocha-Ramírez
authors.forename: Iris
authors.initials: I
authors.lastname: Estrada-García
authors.forename: Luz María
authors.initials: LM
authors.lastname: López-Marín
authors.forename: Erika
authors.initials: E
authors.lastname: Segura-Salinas
authors.forename: Patricia
authors.initials: P
authors.lastname: Méndez-Aragón
authors.forename: Dick
authors.initials: D
authors.lastname: Van Soolingen
authors.forename: Rubén
authors.initials: R
authors.lastname: Torres-González
authors.forename: Rommel
authors.initials: R
authors.lastname: Chacón-Salinas
authors.forename: Sergio
authors.initials: S
authors.lastname: Estrada-Parra
authors.forename: Carmen
authors.initials: C
authors.lastname: Maldonado-Bernal
authors.forename: Constantino
authors.initials: C
authors.lastname: López-Macías
authors.forename: Armando
authors.initials: A
authors.lastname: Isibasi
mesh_terms: D016207:Cytokines / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D008055:Lipids / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014774:Virulence
chemical_list: D016207:Cytokines; D006684:HLA-DR Antigens; D008055:Lipids; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4