title: Expression of the Mycobacterium tuberculosis PPE37 protein in Mycobacterium smegmatis induces low tumour necrosis factor alpha and interleukin 6 production in murine macrophages.
abstract: PPE37 is a member of the Mycobacterium tuberculosis proline-proline-glutamic acid (PPE) multigene family. Its expression is upregulated in bacteria that are phagocytosed by macrophages and is enhanced even more in bacteria isolated from the lungs of infected mice. This raises the possibility that PPE37 may play a role in the virulence of M. tuberculosis and led to this investigation of the function of PPE37. Recombinant bacterial strains, one expressing the M. tuberculosis PPE37 protein (Ms_ppe37) and another harbouring the vector alone (Ms_vec) were generated from the non-pathogenic Mycobacterium smegmatis. These bacterial strains were used to infect peritoneal exudate and bone marrow-derived macrophages. It was found that, despite the comparable intracellular survival between the two recombinant M. smegmatis strains, Ms_ppe37 induced a significantly lower level of tumour necrosis factor alpha and interleukin 6 in the infected macrophages compared with Ms_vec. Western blot analyses revealed that the activation levels of nuclear factor kappa B, mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase and MAPK/p38 were lower in macrophages infected with Ms_ppe37 than in macrophages infected with Ms_vec. These results suggest that PPE37 may have a potential role in interfering with the pro-inflammatory cytokine response of infected macrophages.
authors.affiliation: Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Daim
authors.affiliation: Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kawamura
authors.affiliation: Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Tsuchiya
authors.affiliation: Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hara
authors.affiliation: Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kurenuma
authors.affiliation: Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Sita R
authors.initials: SR
authors.lastname: Dewamitta
authors.affiliation: Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Sakai
authors.affiliation: Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Nomura
authors.affiliation: Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Huixin
authors.initials: H
authors.lastname: Qu
authors.affiliation: Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Mitsuyama
mesh_terms: D000818:Animals; D000940:Antigenic Variation; D000942:Antigens, Bacterial / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology*; D001483:Base Sequence; D016923:Cell Death; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D005798:Genes, Bacterial; D005822:Genetic Vectors; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D020102:Mycobacterium smegmatis / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D011995:Recombination, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D014774:Virulence / Q000235:genetics / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha