The immunostimulant RU41740 from Klebsiella pneumoniae activates human cells in whole blood to potentially stimulate innate and adaptive immune responses

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-α 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-α. IFN-γ, 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.