LE STUDIUM / Marie Skłodowska-Curie Research Fellowship
In residence at
Dr Valérie Quesniaux
Study of pulmonary damage in experimental severe Malariav: Malaria-Associated acute respiratory distress syndrome (MA-ARDS) and Malaria Sepsis Induced by secondary bacterial infection
Plasmodium parasites annually infect hundreds of millions of people and complications known as severe malaria lead to half a million deaths. Severe malaria includes cerebral malaria (CM), acute respiratory distress syndrome (ARDS), and severe anemia. Experimental cerebral malaria induced by P. berghei ANKA infection is a relevant model to study some severe malaria-related manifestations. However, the rapid death of infected animals deeply limits the study of other malaria-associated syndromes.
In this study, we propose to investigate the immunopathology of two pulmonary often-lethal major but neglected complications: malaria-associated acute respiratory distress syndrome (MA-ARDS) and malaria sepsis induced by secondary bacterial infection.
First, we aim to characterize the endothelial-leukocyte interactions in a new rodent model of MA-ARDS, using C57BL/6 mice infected with P. berghei NK65. We hypothesize that CD8+ T cells display a detrimental role in the context of pulmonary endothelial interaction and damage, through the involvement of adhesion molecules (LFA-1 and VLA-4) and granzyme release, respectively. Since septic disorders are associated with the development of ARDS, we are planning in a second part to examine the mechanisms of pulmonary damage in the context of secondary bacterial challenge, focusing on the role of free heme-associated cell death.
Together, this study will add significant data in regards to malaria-associated pulmonary syndromes. A complete understanding of the complexity and diversity of severe malaria complications is essential for the development of new therapeutic approaches.