Plasmodium yoelii Uses a TLR3-Dependent Pathway to Achieve Mammalian Host Parasitism

J Immunol. 2020 Dec 1;205(11):3071-3082. doi: 10.4049/jimmunol.1901317. Epub 2020 Nov 4.


Malaria is associated with complicated immunopathogenesis. In this study, we provide evidence for an unexpected role of TLR3 in promoting the establishment of Plasmodium yoelii infection through delayed clearance of parasitemia in wild type C57BL/6jRj (B6) compared with TLR3 knockout mice. In this study, we confirmed an increased expression of Tlr3, Trif, Tbk1, and Irf7/Irf3 in the liver 42 h postinfection and the initiation of an early burst of proinflammatory response such as Ifng, NF-kB, and Tnfa in B6 mice that may promote parasite fitness. Interestingly, in the absence of TLR3, we showed the involvement of high IFN-γ and lower type I IFN response in the early clearance of parasitemia. In parallel, we observed an increase in splenic NK and NKT cells expressing TLR3 in infected B6 mice, suggesting a role for TLR sensing in the innate immune response. Finally, we find evidence that the increase in the frequency of CD19+TLR3+ B cells along with reduced levels of total IgG in B6 mice possibly suggests the initiation of TLR3-dependent pathway early during P. yoelii infection. Our results thus reveal a new mechanism in which a parasite-activated TLR3 pathway promotes blood stage infection along with quantitative and qualitative differences in Ab responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • Immunity, Innate / immunology
  • Immunoglobulin G / immunology
  • Inflammation / immunology
  • Inflammation / parasitology
  • Interferon Type I / immunology
  • Interferon-gamma / immunology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / parasitology
  • Malaria / immunology*
  • Malaria / parasitology
  • Mammals / immunology*
  • Mammals / parasitology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B / immunology
  • Natural Killer T-Cells / immunology
  • Natural Killer T-Cells / parasitology
  • Parasitemia / immunology
  • Plasmodium yoelii / immunology*
  • Signal Transduction / immunology
  • Toll-Like Receptor 3 / immunology*
  • Tumor Necrosis Factor-alpha / immunology


  • Immunoglobulin G
  • Interferon Type I
  • NF-kappa B
  • TLR3 protein, mouse
  • Toll-Like Receptor 3
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma