The role of CD39 ectonucleotidase in acute respiratory distress syndrome associated with pulmonary malaria

• Grant number: 22/00858-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2022
• End date: November 30, 2023
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Maria Regina D'Império Lima
• Grantee: Luciana dos Santos Barros Manhães
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 15/20432-8 - Intervention in signaling pathways associated with the recognition of cellular damage to reduce the pathology of severe forms of malaria and tuberculosis, AP.TEM

Abstract

Acute Respiratory Distress Syndrome (ARDS) results from acute lung injury (ALI) mainly caused by infectious lung diseases. The breakdown of the alveolar-capillary barrier results in increased vascular permeability, leakage of fluid into the interstitial space of the lung, and hypoxia. This phenomenon is reported in pulmonary malaria which cytokine storm and CD8+ T lymphocytes can destroy the vascular endothelium. In this context, we postulate that CD39 ectonucleotidase may have an important regulatory role, cleaving ATP released during cell damage and the acute inflammatory response and generating adenosine that has anti-inflammatory activity. Thus, the general objective of this project is to determine the role of the CD39 enzyme in the development of pulmonary malaria. As an experimental model, the pulmonary disease caused by Plasmodium berghei NK65 will be evaluated in C57BL/6 and ENTPD1-/- mice, as well as in CD8-/- animals adoptively transferred with CD8+ T lymphocytes devoid or not of this molecule. The parameters to be analyzed will be the parasitaemia, survival curve, serum concentration of endothelial growth factor (VEGF), pause and respiratory rate, as well as histology, permeability and leukocyte composition of the lungs. Therefore, the pathogenesis of pulmonary malaria and its immunological mechanisms need to be better understood to contribute to the development of target-specific therapies.