The TLR2 signaling pathway is activated by sporozoites and suppresses intrahepatic parasite development (MPF3P.815)

Abstract

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 find that sporozoite lysate can significantly activate TLR2. Further studies show that sporozoite lysate can be recognized by either TLR2 homodimers or TLR2/1 and TLR2/6 heterodimers and induce macrophages to release proinflammatory cytokines in a TLR2-dependent manner. Interestingly, the TLR2 signaling pathway can significantly suppress the development of the pre-erythrocytic stage, and the administration of TLR2 agonists greatly reduced the liver parasite load of mice challenged with sporozoites. Additionally, the observed higher level of parasite burden in TLR2-/- mice is 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 pathway, which in turn significantly inhibits the intrahepatic parasites. This may not only help us to understand the mechanism of the innate immune response against pre-erythrocytic stage of malaria parasite but may also provide us with novel clues to design preventive anti-malaria therapies.