title: The B subunit of Escherichia coli heat-labile toxin alters the development and antigen-presenting capacity of dendritic cells.
abstract: Escherichia coli's heat-labile enterotoxin (Etx) and its non-toxic B subunit (EtxB) have been characterized as adjuvants capable of enhancing T cell responses to co-administered antigen. Here, we investigate the direct effect of intravenously administered EtxB on the size of the dendritic and myeloid cell populations in spleen. EtxB treatment appears to enhance the development and turnover of dendritic and myeloid cells from precursors within the spleen. EtxB treatment also gives a dendritic cell (DC) population with higher viability and lower activation status based on the reduced expression of MHC-II, CD80 and CD86. In this respect, the in vivo effect of EtxB differs from that of the highly inflammatory mediator lipopolysaccharide. In in vitro bone marrow cultures, EtxB treatment was also found to enhance the development of DC from precursors dependent on Flt3L. In terms of the in vivo effect of EtxB on CD4 and CD8 T cell responses in mice, the interaction of EtxB directly with DC was demonstrated following conditional depletion of CD11c(+) DC. In summary, all results are consistent with EtxB displaying adjuvant ability by enhancing the turnover of DC in spleen, leading to newly mature myeloid and DC in spleen, thereby increasing DC capacity to perform as antigen-presenting cells on encounter with T cells.
authors.affiliation: Research School of Biology, Australian National University, Canberra, ACT, Australia.
authors.forename: Jing
authors.initials: J
authors.lastname: Ji
authors.affiliation: Research School of Biology, Australian National University, Canberra, ACT, Australia.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Griffiths
authors.affiliation: John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Milburn
authors.affiliation: John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Hirst
authors.affiliation: Faculty of Health Sciences and Medicine, Bond University, Gold Coast, QLD 4229, Australia.
authors.forename: Helen C
authors.initials: HC
authors.lastname: O'Neill
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D001427:Bacterial Toxins / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004768:Enterotoxins / Q000494:pharmacology*; D029968:Escherichia coli Proteins / Q000494:pharmacology*; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology; D021122:Protein Subunits / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D021122:Protein Subunits; C084881:flt3 ligand protein; C027538:heat-labile enterotoxin, E coli
keywords: T cells; adjuvant; cell activation; dendritic cells; enterotoxin