title: The TLR2 is activated by sporozoites and suppresses intrahepatic rodent malaria parasite development.
abstract: TLRs (Toll-like receptors) play an important role in the initiation of innate immune responses against invading microorganisms. Although several TLRs have been reported to be involved in the innate immune response against the blood-stage of malaria parasites, the role of TLRs in the development of the pre-erythrocytic stage is still largely unknown. Here, we found that sporozoite and its lysate could significantly activate the TLR2, and induce macrophages to release proinflammatory cytokines, including IL-6, MCP-1 and TNF-α, in a TLR2-dependent manner. Further studies showed that sporozoite and its lysate could be recognized by either TLR2 homodimers or TLR2/1 and TLR2/6 heterodimers, implicating the complexity of TLR2 agonist in sporozoite. Interestingly, the TLR2 signaling can significantly suppress the development of the pre-erythrocytic stage of Plasmodium yoelii, as both liver parasite load and subsequent parasitemia were significantly elevated in both TLR2- and MyD88-deficient mice. Additionally, the observed higher level of parasite burden in TLR2(-/-) mice was found to be closely associated with a reduction in proinflammatory cytokines in the liver. Therefore, we provide the first evidence that sporozoites can activate the TLR2 signaling, which in turn significantly inhibits the intrahepatic parasites. This may provide us with novel clues to design preventive anti-malaria therapies.
authors.affiliation: Department of Pathogenic Biology, Third Military Medical University, Chongqing, 400038, P. R. China.|Institute of Immunology of PLA, Third Military Medical University, Chongqing, 400038, P. R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Pathogenic Biology, Third Military Medical University, Chongqing, 400038, P. R. China.
authors.forename: Zhangping
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Department of Pathogenic Biology, Third Military Medical University, Chongqing, 400038, P. R. China.
authors.forename: TaoLi
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Pathogenic Biology, Third Military Medical University, Chongqing, 400038, P. R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of Pathogenic Biology, Third Military Medical University, Chongqing, 400038, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Pathogenic Biology, Third Military Medical University, Chongqing, 400038, P. R. China.
authors.forename: Taiping
authors.initials: T
authors.lastname: Liu
authors.affiliation: Institute of Immunology of PLA, Third Military Medical University, Chongqing, 400038, P. R. China.
authors.forename: Yuzhang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pathogenic Biology, Third Military Medical University, Chongqing, 400038, P. R. China.
authors.forename: Wenyue
authors.initials: W
authors.lastname: Xu
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D018836:Inflammation Mediators / Q000378:metabolism; D008109:Liver Diseases, Parasitic; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D008288:Malaria / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology*; D051379:Mice; D018345:Mice, Knockout; D059208:Parasite Load; D010961:Plasmodium / Q000502:physiology*; D010967:Plasmodium yoelii; D034101:Sporozoites; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D051195:Toll-Like Receptor 2