title: BCG promotes cord blood monocyte-derived dendritic cell maturation with nuclear Rel-B up-regulation and cytosolic I kappa B alpha and beta degradation.
abstract: Mycobacterium bovis bacillus Calmette-Guerin (BCG) is given to millions of neonates in developing countries as a vaccine against Mycobacterium tuberculosis; however, little is known about the initiation of response in neonatal dendritic cells (DCs) to BCG. To address this issue, the interaction of BCG with human cord blood monocyte-derived DCs was studied. We showed that BCG could promote cord blood monocyte-derived DC maturation by up-regulation of CD80, CD83, CD86, CD40, and MHC class II molecules and down-regulation of mannose receptor. BCG was able to induce similar levels of tumor necrosis factor-alpha and IL-10 but no bioactive IL-12p70 production from cord blood DCs as from adult blood DCs. Functionally BCG-treated cord blood DCs had higher ability to induce mixed lymphocyte reaction than non-BCG-treated cord blood DCs. Both non-BCG-treated and BCG-treated cord blood DCs efficiently induced a high level of IL-10, medium level of interferon-gamma, but little IL-4 production by cord blood naïve CD4+ T cells. Heat shock protein 65, a key component of BCG, had no effect on cord blood DC maturation in terms of CD86, MHC class II, and mannose receptor up-regulation. During the BCG-induced maturation process of cord blood DCs, nuclear transcription factor Rel-B was up-regulated and cytosolic Rel-B down-regulated with cytosolic IkappaB alpha and beta degradation. These results suggest that BCG can promote cord blood monocyte-derived DC maturation, and that the mechanism is through the up-regulation of nuclear Rel-B secondary to the degradation of cytosolic IkappaB alpha and beta.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China. lauylung@hkucc.hku.hk
authors.forename: Enmei
authors.initials: E
authors.lastname: Liu
authors.forename: Helen K W
authors.initials: HK
authors.lastname: Law
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
mesh_terms: D000328:Adult; D000906:Antibodies / Q000494:pharmacology; D001426:Bacterial Proteins / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D018834:Chaperonin 60; D018833:Chaperonins / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism*; D015536:Down-Regulation; D005312:Fetal Blood; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D015847:Interleukin-4 / Q000378:metabolism; D009000:Monocytes / Q000166:cytology*; D009163:Mycobacterium bovis; D000072000:NF-KappaB Inhibitor alpha; D021122:Protein Subunits / Q000097:blood; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000906:Antibodies; D001426:Bacterial Proteins; D018834:Chaperonin 60; D000949:Histocompatibility Antigens Class II; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D021122:Protein Subunits; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C074119:heat-shock protein 65, Mycobacterium; D016753:Interleukin-10; D000072000:NF-KappaB Inhibitor alpha; D051841:Transcription Factor RelB; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D018833:Chaperonins