title: Differential effects of Francisella tularensis lipopolysaccharide on B lymphocytes.
abstract: Francisella tularensis, a designated Category A biological agent, can cause severe infection in humans. Previous studies have demonstrated a significant immunoprotective role for B lymphocytes in animal models, but the responses of human B lymphocytes to F. tularensis components are largely unknown. The LPS of F. tularensis is atypical and has been reported to lack biological activity on myeloid cells and mouse B cells. Our study characterized the immunological effects of highly purified LPS from different stains of F. tularensis on human B lymphocytes and compared these effects with those on mouse B cells and human monocyte-derived macrophages. Results indicate that marked differences exist between cell type and species in specific responses to this interesting bacterial component. In sharp contrast to responses of mouse splenic B cells or human macrophages, human peripheral B cells showed reproducibly elevated IL-6, TNF-alpha, and antibody production in response to F. tularensis LPS. Data also indicated that these activated human B lymphocytes may subsequently promote the activation of other immune cell types by direct cell-cell interaction. Further investigation into the potential usefulness of F. tularensis LPS as an adjuvant component of a more optimal subunit vaccine is warranted, as it is now clear that it is not biologically inactive, as assumed previously.
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Riad M
authors.initials: RM
authors.lastname: Rahhal
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Vanden Bush
authors.forename: Molly K
authors.initials: MK
authors.lastname: McLendon
authors.forename: Michael A
authors.initials: MA
authors.lastname: Apicella
authors.forename: Gail A
authors.initials: GA
authors.lastname: Bishop
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001694:Biological Warfare; D002460:Cell Line; D005604:Francisella tularensis / Q000737:chemistry; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D008070:Lipopolysaccharides / Q000737:chemistry / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D018448:Models, Immunological; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D022223:Vaccines, Subunit / Q000737:chemistry / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D022223:Vaccines, Subunit