The Eph/Ephrin molecules are modulated in organs of parasitized red blood cells sequestration and may contribute to disease pathogenesis in rodent malaria. (P3059)

Abstract

Abstract Eph receptors and their Ephrin ligands are the largest family of receptor tyrosine kinases. Beyond their role in cell trafficking/adhesion and cancer, nothing is known about their activation during malaria infection. We explored the regulation of Eph/Ephrin in malaria using the rodent malaria model P. berghei ANKA, a parasite that causes experimental cerebral malaria in C57BL/6 mice. Infection with P. berghei ANKA leads to modulation of transcription for some members of the Eph/Ephrin in C57BL/6 mouse brain and spleen. This may be driven by inflammatory cytokines upregulated in these organs in response to sequestration of iRBCs because TNFR2-/- mice which are known to be resistant from death by ECM did not display any upregulation of Eph/Ephrin. To further examine their modulation, subsets of antigen presenting cells and T cells were FACS sorted from splenocytes at different time points post infection. Transcription was found to be modulated between days 2 and 3, particularly for EphB2 on CD11b+ macrophage/neutrophil subset. To support the modulation of transcription in the brain during ECM, mouse primary brain microvascular endothelial cells were isolated from naïve mice and stimulated with inflammatory cytokines and lysates of iRBCs. We observed an increase in the transcription of EphB4 and EphB6 in response to inflammatory cytokine signaling and an increase in the protein expression of EphB4 in response to iRBC lysates. The implications of these results will be discussed.