Murine cerebral malaria development is independent of toll-like receptor signaling.
Malaria pigment hemozoin was reported to activate the innate immunity by Toll-like receptor (TLR)-9 engagement. However, the role of TLR activation for the development of cerebral malaria (CM), a lethal complication of malaria infection in humans, is unknown. Using Plasmodium berghei ANKA (PbA) infection in mice as a model of CM, we report here that TLR9-deficient mice are not protected from CM. To exclude the role of other members of the TLR family in PbA recognition, we infected mice deficient for single TLR1, -2, -3, -4, -6, -7, or -9 and their adapter proteins MyD88, TIRAP, and TRIF. In contrast to lymphotoxin alpha-deficient mice, which are resistant to CM, all TLR-deficient mice were as sensitive to fatal CM development as wild-type control mice and developed typical microvascular damage with vascular leak and hemorrhage in the brain and lung, together with comparable parasitemia, thrombocytopenia, neutrophilia, and lymphopenia. In conclusion, the present data do not exclude the possibility that malarial molecular motifs may activate the innate immune system. However, TLR-dependent activation of innate immunity is unlikely to contribute significantly to the proinflammatory response to PbA infection and the development of fatal CM.
Togbe
Dieudonnée
D
Molecular Immunology and Embryology, Centre National de la Recherche Scientifique, and University of Orleans, Transgenose Institute, Orleans, France.
Schofield
Louis
L
Grau
Georges E
GE
Schnyder
Bruno
B
Boissay
Victorine
V
Charron
Sabine
S
Rose
Stéphanie
S
Beutler
Bruce
B
Quesniaux
Valérie F J
VF
Ryffel
Bernhard
B
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000469:parasitology / Q000473:pathology; D002196:Capillaries / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000098:blood supply / Q000469:parasitology / Q000473:pathology; D008168:Lung / Q000098:blood supply / Q000469:parasitology / Q000473:pathology; D016779:Malaria, Cerebral / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D010962:Plasmodium berghei; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors / Q000378:metabolism*
D051193:Toll-Like Receptors