title: The immunostimulant RU41740 from Klebsiella pneumoniae activates human cells in whole blood to potentially stimulate innate and adaptive immune responses.
abstract: The compound RU41740 from Klebsiella pneumoniae, when used as an immunostimulant, improves responses to bacterial and yeast infections in murine models and in human trials. The aim of this study was to determine in vitro, the capacity of RU41740 to stimulate human leukocytes in whole blood. Blood samples from healthy adult donors were incubated with RU41740 for 4 or 24 h and leukocytes were assessed for levels of activation markers and cytokine production by flow cytometry and ELISA. The early activation marker CD69 was induced at 4 h in NK cells > B cells > T cells > monocytes whereas at 24 h CD80 and CD86 levels were augmented on monocytes and IL-12 was induced; HLA-DR levels increased on both B cells and monocytes. The pro-inflammatory cytokines TNF-alpha and IL-6 were produced at 4 h at similar levels to that induced by LPS and monocytes appeared to be a source of TNF-alpha. IFN-gamma, was induced at 5 h just in NK cells. Activation induced by RU41740 was not abolished by polymixin B, ruling out the possible contamination with LPS. These data indicate that RU41740 can impact not only the innate immune responses but potentially enhance adaptive immune responses by up-regulating expression of molecules involved in antigen presentation on antigen presenting cells.
authors.affiliation: Departamento de Investigaciones Inmunológicas, Instituto de Diagnóstico y Referencia Epidemiológicos, Secretaría de Salud, México City. sps2@case.edu
authors.forename: Sigifredo
authors.initials: S
authors.lastname: Pedraza-Sánchez
authors.forename: Yolanda
authors.initials: Y
authors.lastname: González-Hernández
authors.forename: Alejandro
authors.initials: A
authors.lastname: Escobar-Gutiérrez
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Ramachandra
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D001426:Bacterial Proteins / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects; D007711:Klebsiella pneumoniae / Q000737:chemistry*; D037181:Lectins, C-Type; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011112:Polymyxin B / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099192:CD69 Antigens
chemical_list: D000276:Adjuvants, Immunologic; D000900:Anti-Bacterial Agents; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D001426:Bacterial Proteins; D006684:HLA-DR Antigens; D015850:Interleukin-6; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D011112:Polymyxin B; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens; C037567:glycoprotein, Klebsiella pneumoniae