Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism

Leptospira interrogans are zoonotic pathogens that have been linked to a re cent increased incidence of morbidity and mortality in highly populated tro pical urban centers. They are unique among invasive spirochetes in that the y contain outer membrane lipopolysaccharide (LPS) as well as lipoproteins. Here we show that both these leptospiral outer membrane constituents activa te macrophages through CD14 and the Toll-like receptor 2 (TLR2). Conversely , it seems that TLR4, a central component for recognition of Gram-negative LPS, is not involved in cellular responses to L. interrogans. We also show that for intact L. interrogans, it is LPS, not lipoprotein, that constitute s the predominant signaling component for macrophages through a TLR2 pathwa y. These data provide a basis for understanding the innate immune response caused by leptospirosis and demonstrate a new ligand specificity for TLR2.