title: Mycobacterium tuberculosis PE25/PPE41 protein complex induces activation and maturation of dendritic cells and drives Th2-biased immune responses.
abstract: Mycobacterium tuberculosis evades innate host immune responses by parasitizing macrophages and causes significant morbidity and mortality around the world. A mycobacterial antigen that can activate dendritic cells (DCs) and elicit effective host innate immune responses will be vital to the development of an effective TB vaccine. The M. tuberculosis genes PE25/PPE41 encode proteins which have been associated with evasion of the host immune response. We constructed a PE25/PPE41 complex gene via splicing by overlapping extension and expressed it successfully in E. coli. We investigated whether this protein complex could interact with DCs to induce effective host immune responses. The PE25/PPE41 protein complex induced maturation of isolated mouse DCs in vitro, increasing expression of cell surface markers (CD80, CD86 and MHC-II), thereby promoting Th2 polarization via secretion of pro-inflammatory cytokines IL-4 and IL-10. In addition, PE25/PPE41 protein complex-activated DCs induced proliferation of mouse CD4(+) and CD8(+) T cells, and a strong humoral response in immunized mice. The sera of five TB patients were also highly reactive to this antigen. These findings suggest that interaction of the PE25/PPE41 protein complex with DCs may be of great immunological significance.
authors: Laboratory of Infection and Immunity, School of Basic Medical Sciences, Sichuan University, Chengdu, 610041, China.
authors: Wei
authors: W
authors: Chen
authors: Department of Urology, West China Hospital, Sichuan University, Chengdu, China.
authors: Yige
authors: Y
authors: Bao
authors: Department of Respiratory Disease and Tuberculosis, West China Hospital, Sichuan University, Chengdu, China.
authors: Xuerong
authors: X
authors: Chen
authors: Division of Urology, Department of Surgery, The University of Western Ontario, London, Canada.|Department of Microbiology and Immunology, The University of Western Ontario, London, Canada.|Canadian Centre for Human Microbiome and Probiotics, Lawson Health Research Institute, London, Canada.
authors: Jeremy
authors: J
authors: Burton
authors: Laboratory of Infection and Immunity, School of Basic Medical Sciences, Sichuan University, Chengdu, 610041, China.
authors: Xueli
authors: X
authors: Gong
authors: Laboratory of Infection and Immunity, School of Basic Medical Sciences, Sichuan University, Chengdu, 610041, China.
authors: Dongqing
authors: D
authors: Gu
authors: Laboratory of Infection and Immunity, School of Basic Medical Sciences, Sichuan University, Chengdu, 610041, China.
authors: Youjun
authors: Y
authors: Mi
authors: Laboratory of Infection and Immunity, School of Basic Medical Sciences, Sichuan University, Chengdu, 610041, China. baolang@scu.edu.cn.
authors: Lang
authors: L
authors: Bao
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D000954:Antigens, Surface / Q000378:metabolism; D001426:Bacterial Proteins / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D056724:Immunity, Humoral; D007114:Immunization; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology*
chemical_list: D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001426:Bacterial Proteins; D016207:Cytokines; D016328:NF-kappa B; D011994:Recombinant Proteins
keywords: Dendritic cell; Immune response; Mycobacterium tuberculosis; PE25/PPE41 protein complex; Th2 polarization