title: BCG vaccine mediated reduction in the MHC-II expression of macrophages and dendritic cells is reversed by activation of Toll-like receptors 7 and 9.
abstract: Tuberculosis is a major cause of death in mankind and BCG vaccine protects against childhood but not adult tuberculosis. BCG avoids lysosomal fusion in macrophages decreasing peptides required for activating CD4 T cells and Th1 immunity while suppressing the expression of MHC-II by antigen presenting cells (APCs). An in vitro model of antigen presentation showed that ligands for TLR-9, 7, 4 and 1/2 increased the ability of APCs to present antigen-85B of BCG to CD4 T cells, which correlated with an increase in MHC-II expression. TLR-activation led to a down-regulation of MARCH1 ubiquitin ligase which prevents the degradation of MHC-II and decreased IL-10 also contributed to an increase in MHC-II. TLR-activation induced up-regulation of MHC-II was inhibited by the blockade of IRAK, NF-kB, and MAPKs. TLR-7 and TLR-9 ligands had the most effective adjuvant like effect on MHC-II of APCs which allowed BCG vaccine mediated activation of CD4 T cells.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, TX 77030, USA.
authors.forename: Pearl
authors.initials: P
authors.lastname: Bakhru
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, TX 77030, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Sirisaengtaksin
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, TX 77030, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Soudani
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, TX 77030, USA.
authors.forename: Seema
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, TX 77030, USA.
authors.forename: Arshad
authors.initials: A
authors.lastname: Khan
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, TX 77030, USA. Electronic address: Chinnaswamy.Jagannath@uth.tmc.edu.
authors.forename: Chinnaswamy
authors.initials: C
authors.lastname: Jagannath
mesh_terms: D000217:Acyltransferases / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000942:Antigens, Bacterial / Q000276:immunology / Q000494:pharmacology; D001500:BCG Vaccine; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics; D051199:Toll-Like Receptor 7 / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D014376:Tuberculosis / Q000276:immunology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: C510665:19K antigen, Mycobacterium tuberculosis; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; C050016:lipoarabinomannan; D016753:Interleukin-10; D000217:Acyltransferases; C119774:antigen 85C, Mycobacterium tuberculosis; C545340:MARCH1 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: Antigen processing; BCG vaccine; CD80; CD86; Dendritic cells; IL-10; MARCH1 ubiquitin ligase; MHC-II; Macrophage; Toll-like receptor (TLR)