Determination of haplotypes of CXCL12-CXCR4/CXCR7 axis genes in malaria patients from Brazil and Africa

• Grant number: 09/05738-2
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2009
• End date: September 30, 2012
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Heitor Franco de Andrade Junior
• Grantee: Heitor Franco de Andrade Junior
• Host Institution: Instituto de Medicina Tropical de São Paulo (IMT). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Malaria, one of the main endemic diseased in the World, courses with varied severity, associated either to parasite or host factors. Caused by the same parasite, in special P. falciparum, the disease appears to have no specific parasitic determinants for severity of human disease. Malaria control is dependent of harmonic amplification of spleen structure and adequate immune response, mediated by chemokines. We studied the role of the chemokine CXCL12 in rodent malaria models, determining that adequate homing of CD11c+ cells is associated with mild disease in P. chabaudi mice infection, and CXCL12supplementation may restore host resistance in lethal models. This chemokine is recognizedby its receptor CXCR4 in lymphoid and hematopoetic cells. In HIV infection, as CXCR4 is a co-receptor of this virus, CXCR4 and CXCL12 haplotypes are related to disease progression and outcome. Certain haplotypes are associated with worst HIV progression and are higher prevalent in Africa, where it could be selected by intense malaria infection. Recently, a new receptor for CXCL12, the CXCR7, was described, with vascular and inflammatory function. We devised to study the alleles frequency for CXCL12-CXCR4/CXCR7 axis genes those genes in Brazilian and African malaria patients, relating those frequency to malaria severity. (AU)