The role of endothelial cells in the immunopathogenesis of ALI / ARDS associated with murine malaria: effects and mechanisms

Malaria is one of the biggest global health problems, especially in tropical and subtropical regions. In Brazil, 99% of cases are concentrated in the Legal Amazon, where infections by Plasmodium vivax are the main causes of the disease and can be fatal. Plasmodium ssp. can lead to a severe respiratory condition, with pulmonary complications called acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Pulmonary complications are characterized by decreased capacity for gas exchange, increased leukocyte activity and increased inflammatory mediators in the lungs. The large number of factors potentially involved and associated with the great difficulties in studying the disease in humans means that the molecular basis of this pulmonary dysfunction remains poorly understood, leading to high mortality in health units. Mechanisms linked to innate immunity have been shown to be important for the early control of Plasmodium infection, through the increase of cytokines and activation of the cellular immune response. However, an excessive and/or prolonged inflammatory response contributes to the pathogenesis and symptoms associated with severe malaria. Receptors for Toll-like molecular patterns play a critical role in detecting pathogens and activating the innate immune response. Another relevant aspect that may be associated with the development of severe malaria is the ability of parasitized erythrocytes to be sequestered in the microvasculature of tissues, resulting in activation of pulmonary endothelial cells and increased pulmonary vascular permeability. Knowledge of aspects of the innate immune response will make an important contribution to the understanding of ALI/ARDS associated with malaria, in addition to enabling studies aimed at developing new methodologies for treating the disease.

Project Details

Basic Science
Immunology

Feb 2015 — Jan 2017

Brazil