Evaluation and manipulation of oxygen tension in cellular and tissular microenvironments during infectious processes

Abstract

The microenvironment of diseased tissues with prolonged periods of reduced blood flow, vasoconstriction and cellular proliferation has a reduced oxygen tension (hypoxia). Hypoxia in chronic lesions and tumors results in inflammation and delay of cure and therapies effect. The involvement of hypoxia in infectious diseases is less studied. This project is the continuity of our studies, including other pathogens besides Leishmania, and it has two lines of investigation already consolidated in the lab: the first search hypoxia cause/effect during pathophysiological phenomena and the second line analyses hyperbaric treatment effects. The experimental models will be of diseases caused for L. amazonensis, Schistosoma mansoni, Plasmodium berghei and Pseudomonas aeruginosa. Specifically we intend: to evaluate HIF (hypoxia inducible factor) expression, hypoxia and several molecular markers, during murine leishmaniasis, cerebral malaria and schistosomiasis; the use of L. amazonensis-GFP, autophagy in macrophages infected with L. amazonensis, and to optimize protocols of hyperbaric oxygenation treatment and to study its mechanism during murine leishmaniasis, cerebral malaria and infection with P. aeruginosa with burn induction. Understanding cellular and tisular responses to hypoxia will be possible identify therapeutic targets and optimize combinations of new and already established treatments. The exploration of reoxygenation strategy and the explanation of its mechanism will be useful to establish protocols of treatment for pathologies associated to hypoxia. (AU)