CXCR3 determines strain susceptibility to murine cerebral malaria by mediating T lymphocyte migration toward IFN-γ-induced chemokines

Philippe E. Van den Steen, Katrien Deroost, Ilse Van Aelst, Nathalie Geurts, Erik Martens, Sofie Struyj, Catherine Q. Nie, Diana S. Hansen, Patrick Matthys, Jo Van Damme, Ghislain Opdenakker

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60 Citations (Scopus)

Abstract

Cerebral malaria (CM) results from the binding of infected erythrocytes and leukocytes to brain endothelia. The precise mechanisms underlying lymphocyte recruitment and activation in CM remain unclear. Therefore, the expression of various chemokines was quantified in brains of mice infected with Plasmodium berghei ANKA (PbA). Several chemokines attracting monocytes and activated T-lymphocytes were expressed at high levels. Their expression was almost completely abrogated in IFN-γ ligand and receptor KO mice, indicating that IFN-γ is an essential chemokine inducer in vivo. Surprisingly, the expression levels of chemokines, IFN-γ and also adhesion molecules in the brain were not lower in CM-resistant Balb/c and DBA/2 mice compared to CM-sensitive C57BL/6 and DBA/1 mice, although T lymphocyte sequestration in the brain was significantly less in CM-resistant than in CM-sensitive mice. This difference correlated with a higher up-regulation of the CXC chemokine receptor (CXCR)-3 on splenic: T cells and a higher chemotactic response to IFN-γ-inducible protein-10 (IP-10) in C57BL/6 compared to Balb/c mice. In conclusion, parasite-induced IFN-γ in the brain results in high local expression levels of specific chemokines for monocytes and lymphocytes. The strain-dependent susceptibility to develop CM is more related to the expression of CXCR3 in circulating leukocytes than to the chemokine expression levels in the brain.

Original languageEnglish
Pages (from-to)1082-1095
Number of pages14
JournalEuropean Journal of Immunology
Volume38
Issue number4
DOIs
Publication statusPublished - Apr 2008
Externally publishedYes

Keywords

  • IFN-γ
  • IP-10
  • Leukocyte sequestration
  • MIG
  • Plasmodium berghei ANKA

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