title: Effect of deletion or overexpression of the 19-kilodalton lipoprotein Rv3763 on the innate response to Mycobacterium tuberculosis.
abstract: The 19-kDa lipoprotein of Mycobacterium tuberculosis is an important target of the innate immune response. To investigate the immune biology of this antigen in the context of the whole bacillus, we derived a recombinant M. tuberculosis H37Rv that lacked the 19-kDa-lipoprotein gene (Delta19) and complemented this strain by reintroduction of the 19-kDa-lipoprotein gene on a multicopy vector to produce Delta19::pSMT181. The Delta19 strain multiplied less well than Delta19::pSMT181 in human monocyte-derived macrophages (MDM) (P = 0.039). Surface expression of major histocompatibility complex class II molecules was reduced in phagocytes infected with M. tuberculosis; this effect was not seen in cells infected with Delta19. Delta19 induced lower interleukin 1beta (IL-1beta) secretion from monocytes and MDM. Overexpression of the 19-kDa protein increased IL-1beta, IL-12p40, and tumor necrosis factor alpha secretion irrespective of phagocyte maturity. These data support reports that the 19-kDa lipoprotein has pleiotropic effects on the interaction of M. tuberculosis with phagocytes. However, this analysis indicates that in the context of the whole bacillus, the 19-kDa lipoprotein is only one of a number of molecules that mediate the innate response to M. tuberculosis.
authors.affiliation: Center for Molecular Microbiology and Infection and Wellcome Trust Center for Research in Clinical Tropical Medicine, Imperial College London, UK.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Stewart
authors.forename: Katalin A
authors.initials: KA
authors.lastname: Wilkinson
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Newton
authors.forename: Susan M
authors.initials: SM
authors.lastname: Sullivan
authors.forename: Olivier
authors.initials: O
authors.lastname: Neyrolles
authors.forename: John R
authors.initials: JR
authors.lastname: Wain
authors.forename: Janisha
authors.initials: J
authors.lastname: Patel
authors.forename: Kara-Lee
authors.initials: KL
authors.lastname: Pool
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Young
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D017353:Gene Deletion; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007375:Interleukin-1 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D053762:Interleukin-12 Subunit p40; D008074:Lipoproteins / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D010586:Phagocytes / Q000276:immunology / Q000382:microbiology; D010587:Phagocytosis / Q000276:immunology*; D021122:Protein Subunits / Q000378:metabolism; D015533:Transcriptional Activation; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D006684:HLA-DR Antigens; D007375:Interleukin-1; D053762:Interleukin-12 Subunit p40; D008074:Lipoproteins; D021122:Protein Subunits; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12