Induction of experimental cerebral malaria is independent of TLR2/4/9.
The contribution of the Toll-like receptor (TLR) cascade to the pathogenesis of cerebral malaria (CM) is controversially discussed. TLR2 and TLR9 were reported to be involved in the induction of CM in a study while recently TLR signaling was shown to be dispensable for the development of CM. Using Plasmodium berghei ANKA (PbA) infection of mice as a model of CM, we demonstrate here that the induction of CM is independent of TLR2, 4 and 9. Using triple TLR2/4/9-deficient mice, we exclude synergistic effects between the single TLRs that have been previously implicated with malaria pathology. In conclusion, this study shows that the activation of the innate immune response and the development of CM is not dependent on the engagement of TLR2/4/9.
Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, 20359 Hamburg, Germany.
Bernd
B
Lepenies
Jakob P
JP
Cramer
Gerd D
GD
Burchard
Hermann
H
Wagner
Carsten J
CJ
Kirschning
Thomas
T
Jacobs
D000818:Animals; D001921:Brain / Q000469:parasitology; D002448:Cell Adhesion; D016616:Cryoultramicrotomy; D004727:Endothelium / Q000276:immunology; D005434:Flow Cytometry; D007113:Immunity, Innate; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D053762:Interleukin-12 Subunit p40 / Q000032:analysis; D020382:Interleukin-18 / Q000032:analysis; D016779:Malaria, Cerebral / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010962:Plasmodium berghei / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology*
D053762:Interleukin-12 Subunit p40; D020382:Interleukin-18; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D018799:Intercellular Adhesion Molecule-1