Suppression of antigen-specific lymphocyte proliferation by Gram-positive bacterial cell walls

It is largely unknown how bacterial cell walls (BCW) modulate human immune responses. In the present work the effect of Gram-positive BCW on lymphocyte proliferation responses towards several microbial antigens (Ag) or mitogens was studied. Gram-positive BCW were derived from four indigenous bacterial strains and from one pathogen (Streptococcus pyogenes). All BCW preparations used non-specifically suppressed the proliferation responses of peripheral blood mononuclear cells (PBMC) against bacterial and viral Ag, but not against mitogens. Both lymphocytes and macrophages or their secreted products mediated the suppressive effects of BCW, which were not IL-10 dependent. Furthermore, the expression of HLA-DR and CD86 on monocytes/macrophages was downregulated by BCW. Unlike in LPS-induced suppression, the CD14 pathway was not used by BCW of Lactobacillus casei (L.c.). The observed results indicate that Gram-positive BCW suppress antigen-specific lymphocyte proliferation through several mechanisms. This non-specific immunosuppression might be a general function of BCW in the bacteria-host interaction, being of importance for bacterial survival and pathogenicity.