Schistosomal-derived lysophosphatidylcholine are involved in eosinophil activation and recruitment through toll-like receptor-2-dependent mechanisms

Abstract

Parasite-derived lipids may play important roles in host-pathogen interactions and escape mechanisms. Herein, we evaluated the role of schistosomal-derived lipids in Toll-like receptor (TLR)-2 and eosinophil activation in Schistosoma mansoni infection. Mice lacking TLR2 exhibited reduced liver eosinophilic granuloma, compared with that of wild-type animals, following S. mansoni infection. Decreased eosinophil accumulation and eosinophil lipid body (lipid droplet) formation, at least partially due to reduced production of eotaxin, interleukin (IL)-5, and IL-13 in S. mansoni-infected TLR2-/- mice, compared with the corresponding production in wild-type mice, was noted. Although no differences were observed in survival rates during the acute schistosomal infection (up to 50 days), increased survival of TLR2-/- mice, compared with survival of wild-type mice, was observed during the chronic phase of infection. Schistosomal lipid extract- and schistosomal-derived lysophosphatidylcholine (lyso-PC)-stimulated macrophages in vitro induced TLR2-dependent NF-kB activation and cytokine production. Furthermore, in vivo schistosomal lyso-PC administration induced eosinophil recruitment and cytokine production, in a mechanism largely dependent on TLR2. Taken together, our results suggest that schistosomal-derived lyso-PC may participate in cytokine production and eosinophil activation through a TLR2-dependent pathway in S. mansoni infection. Moreover, our results suggest that TLR2-dependent inflammatory reaction, cytokine production, and eosinophil recruitment and activation may contribute to the pathogenesis and lethality in the chronic phase of infection. © 2010 by the Infectious Diseases Society of America. All rights reserved.