In this study, we cloned the cDNAs encoding porcine RP105 (poRP105) and porcine MD-1 (poMD-1) from Peyer's patches of adult swine. The complete open reading frames of poRP105 and poMD-1 contain 1986 and 480bp and encode 661 and 159 amino acid residues, respectively. These two proteins were more similar to the human (77.6% and 76.5% amino acid identity) than the mouse counterparts (70.0% and 71.1% amino acid identity). The results of several experiments in cells cotransfected with poRP105 and poMD-1 indicated both lipopolysaccharide and extracellular phosphopolysaccharide from Lactococcus lactis subsp. cremoris (Lc.cremoris) strongly activate nuclear factor-kappaB and induce the expression of various cytokines via RP105. These effects were mediated by phosphatidylinositol 3-kinase and Bruton's tyrosine kinase. Thus, we identified extracellular polysaccharide from Lc.cremoris as an active substance that can induce immune activation via RP105 and MD-1.