Disruption of CD36 impairs cytokine response to Plasmodium falciparum glycosylphosphatidylinositol and confers susceptibility to severe and fatal malaria in vivo

Samir N. Patel, Ziyue Lu, Kodjo Ayi, Lena Serghides, D. Channe Gowda, Kevin C. Kain

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

CD36 is a scavenger receptor that has been implicated in malaria pathogenesis as well as innate defense against blood-stage infection. Inflammatory responses to Plasmodium falciparum GPI (pfGPI) anchors are believed to play an important role in innate immune response to malaria. We investigated the role of CD36 in pfGPI-induced MAPK activation and proinflammatory cytokine secretion. Furthermore, we explored the role of this receptor in an experimental model of acute malaria in vivo. We demonstrate that ERK1/2, JNK, p38, and c-Jun became phosphorylated in pfGPI-stimulated macrophages. In contrast, pfGPI-induced phosphorylation of JNK, ERK1/2, and c-Jun was reduced in Cd36 -/- macrophages and Cd36-/- macrophages secreted significantly less TNF-α in response to pfGPI than their wild-type counterparts. In addition, we demonstrate a role for CD36 in innate immune response to malaria in vivo. Compared with wild-type mice, Cd36-/- mice experienced more severe and fatal malaria when challenged with Plasmodium chabaudi chabaudi AS. Cd36-/- mice displayed a combined defect in cytokine induction and parasite clearance with a dysregulated cytokine response to infection, earlier peak parasitemias, higher parasite densities, and higher mortality rates than wild-type mice. These results provide direct evidence that pfGPI induces TNF-α secretion in a CD36-dependent manner and support a role for CD36 in modulating host cytokine response and innate control of acute blood-stage malaria infection in vivo.

Original languageEnglish (US)
Pages (from-to)3954-3961
Number of pages8
JournalJournal of Immunology
Volume178
Issue number6
DOIs
StatePublished - Mar 15 2007

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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