Potent immunoregulatory effects of Salmonella typhi flagella on antigenic stimulation of human peripheral blood mononuclear cells

A key function of monocytes/macrophages (M phi) is to present antigens to T cells, However, upon interaction with bacteria, M phi lose their ability t o effectively present soluble antigens, This functional loss was associated with alterations in the expression of adhesion molecules and CD14 and a re duction in the uptake of soluble antigen. Recently, we have demonstrated th at Salmonella typhi flagella (STF) markedly decrease CD14 expression and ar e potent inducers of proinflammatory cytokine production by human periphera l blood mononuclear cells (hPBMC), In order to determine whether S, typhi a nd soluble STF also alter the ability of M phi to activate T cells to proli ferate to antigens and mitogens, hPBMC were cultured in the presence of tet anus toroid (TT) or phytohemagglutinin (PHA) and either killed whole-cell S . typhi or purified STF protein. Both whole-cell S. typhi and STF suppresse d proliferation to PHA and TI, This decreased proliferation was not a resul t of increased M phi, production of nitric oxide, prostaglandin E-2, or oxy gen radicals or the release of interleukin-1 beta, tumor necrosis factor al pha, interleukin-6, or interleukin-10 following exposure to STF. However, t he ability to take up soluble antigen, as determined by fluorescein isothio cyanate-labeled dextran uptake, was reduced in cells cultured with STF, Mor eover, there was a dramatic reduction in the expression of CD54 on M phi af ter exposure to STF, These results indicate that whole-cell S. typhi and ST F have the ability to alter in vitro proliferation to soluble antigens and mitogens by affecting M phi function.