Recerca, Eliminació de la malària

Malaria Pathogenesis: Anemia and Cerebral Malaria

Foto: New York University
Data
15/03/2019
Hora
10.00 h
Lloc
Room 14, Faculty of Medicine and Health Sciences (Campus Clínic, UB)
(Casanova, 143) Barcelona
Ponents
Ana Rodríguez (NYU)

Ana Rodríguez, Associated Professor of the Department of Microbiology at the New York University, will give an open seminar on 'Malaria pathogenesis: anemia and cerebral malaria' on 14 May, 2019. The session will last 50 minutes and there will be 10 more minutes for questions and answers.

A main interest of her laboratory is the study of malaria-induced inflammatory pathology. They also study cerebral malaria, a complication of severe malaria that frequently leads to coma and death.

She will also participate in the Chagas Workshop with a talk on new drugs against Chagas disease, on 14 March. In collaboration with GSK, they performed a high through put screening of 2 million compounds for intracellular Trypanosoma cruzi, to find compounds with anti-trypanosomal activities. Selected compounds are being tested for efficacy in mice.

Malaria pathogenesis: anemia and cerebral malaria

Although the development of severe malaria anemia and cerebral malaria are major causes of death in patients, the pathogenesis of these syndromes are not well understood. Our research work in cerebral malaria has uncovered that Plasmodium falciparum weakens brain endothelial cell junctions through the activation of beta-catenin, a protein that is present in the junctions but also activates transcription in these cells. We observed that this process is regulated by angiotensin receptors (AT1 and AT2) that can inhibit the activation of beta-catenin and preserve the integrity of the endothelium. Results in mice experimental models confirm these findings and suggest that angiotensin receptor modulators, which are approved for use in humans, can be used as adjunctive treatment for cerebral malaria.

Severe anemia is another common complication of malaria, which is caused mainly by the loss of uninfected erythrocytes during infection. We have observed that high levels of autoimmune antibodies that are induced by Plasmodium infection. During malaria, autoimmune antibodies recognizing the lipid phosphatidylserine bind to the surface of uninfected erythrocytes facilitating clearance and contributing to anemia. These autoimmune antibodies are generated by an atypical subclass of B cells that is found to be elevated in the blood of malaria patients and also in patients with classic autoimmune disorders. Activation of these B cells does not require T cells and is mediated by three specific signals that are provided during infection: crosslinking of the B cell receptor (by Plasmodium antigens), TLR9 (by parasite DNA) and interferon-gamma (general inflammatory response).