Signal transduction in Plasmodium-red blood cells interactions and in cytoadherence

• Grant number: 11/21918-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: February 01, 2012
• End date: January 31, 2013
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal Investigator: Célia Regina da Silva Garcia
• Grantee: Laura Nogueira da Cruz
• Supervisor: Alister Gordon Craig
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Liverpool School of Tropical Medicine (LSTM), England

Abstract

Plasmodium parasites are able to sense host signals to modulate its function through a complex cellular machinery and membrane receptors (Hotta, Gazarini et al. 2000; Garcia, Markus et al. 2001; Madeira, Galante et al. 2008; Koyama, Chakrabarti et al. 2009). Moreover Ca2+ signaling pathways in Plasmodium are crucial for parasite development and external ATP modulates Plasmodium-RBC interaction and induces increase of intracellular Ca2+ (Julio Levano-Garcia 2011). ATP may also be involved in host induced inflammation which is followed by malaria infection (Clark, Budd et al. 2006). Interestingly, cytoadherence of infected erythrocyte is also regulated by inflammatory response and Plasmodium falciparum proteins such as PfEMP1 binding to CD36 or ICAM-1 host receptors. ICAM-1 is constitutively present on endothelial cells at low levels and its expression is highly increased by pro-inflammatory cytokines such as interleukin-1 (IL-1) and tumour necrosis factor alpha (TNF±) (Pober 2002). It is worth noting that ICAM-1 is involved in JNK signaling pathway that modulates several proteins including bcl-2 family related to apoptosis (Liu and Lin 2005). Another common cytoadherence receptor, CD36, is involved in the PfGPI induced MAPK activation and proinflammatory cytokine secretion. In this manner we aim to investigate Ca2+ signalling modulation by extracellular ATP in Plasmodium and the possible influence of this pathway in apoptosis of adherent endothelial cells by interaction with ICAM-1 (intercellular adhesion molecule-1) or CD36. (AU)