Murine cerebral malaria development is independent of toll-like receptor signaling

Dieudonnée Togbe, Louis Schofield, Georges E. Grau, Bruno Schnyder, Victorine Boissay, Sabine Charron, Stéphanie Rose, Bruce Beutler, Valérie F J Quesniaux, Bernhard Ryffel

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

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 α-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.

Original languageEnglish (US)
Pages (from-to)1640-1648
Number of pages9
JournalAmerican Journal of Pathology
Volume170
Issue number5
DOIs
StatePublished - May 2007

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Togbe, D., Schofield, L., Grau, G. E., Schnyder, B., Boissay, V., Charron, S., Rose, S., Beutler, B., Quesniaux, V. F. J., & Ryffel, B. (2007). Murine cerebral malaria development is independent of toll-like receptor signaling. American Journal of Pathology, 170(5), 1640-1648. https://doi.org/10.2353/ajpath.2007.060889