Mechanistic aspects of P. vivax

Durada

01/01/2017-31/12/2019

Coordinador

Carmen Fernández Becerra/ Hernando A. Del Portillo

Finançadors

MINECO

Pàgina web

http://www.pvrex.com/

Despite the high burden exerted, Plasmodium vivax has been a ‘neglected’ human malaria parasite. In the last decade, anaemia is one the most prevalent severe malaria manifestations worldwide. Recently, we have obtained first unequivocal evidence of the presence of P. vivax parasites in the bone marrow of an infected patient. Moreover, transcriptional analysis of bone marrow aspirates during infection and at convalescence of this same patient demonstrated transcriptional changes of miRNAs related to erythropoiesis. Also, it is known that P. vivax infections cause bone marrow dyserythropoiesis and ineffective erythropoiesis.

Anaemia in malaria is further exacerbated through the destruction of uninfected red blood cells. Destruction of red blood cells is a function of the spleen, our only blood filtering organ. Splenomegaly is a hallmark of human malarial infections and the degree of anaemia is related to the size of the spleen. Moreover, it has been established that in benign red blood cell disorders inducing anaemia, there is extramedullary haematopoiesis in this organ to compensate for the lack of red blood cells.

Through this proposal our aim is to demonstrate:

(i) that P. vivax invades the bone marrow and causes dyserythropiesis and ineffective erythropoiesis through transcriptional changes;

(ii) that to compensate for this anaemia, bone-marrow derived exosomes from infections signals spleen reticular cells to create hematopoietic niches facilitating extramedullary haematopoiesis in this organ.

Total funding

205,700.00 €