Abstract
Dead cells as a result of tissue damage are quickly engulfed, but before disappearing, warn the surrounding cells so that repair programs are activated. The recognition of cell damage by the innate immune system contributes to the development of inflammatory immune responses and tissue repair, but may also exacerbate tissue injuries. In some cases, uncontrolled cell death can trigger a cascade of destructive processes that ultimately amplifies tissue damage and worsens the disease prognosis. The aim of this project is to characterize the receptors of cellular damage signals that are involved in the progression of severe forms of experimental malaria and tuberculosis, seeking to interfere in these signaling pathways in order to improve disease outcomes. These infectious diseases are among the most prevalent in humans, and together account for more than one million deaths annually worldwide. Another purpose of this project is to evaluate the role of signs of damage in the development of acquired immune response during these infectious diseases. This study can bring an essential knowledge for the development of new therapeutic approaches that can be applied, in conjunction with those already used, in the treatment of severe forms of malaria and tuberculosis, as well as in other diseases (infectious or not) that are characterized by extensive tissue damage. In addition, this study may uncover new molecular mechanisms involved in the recognition of cellular damage and, therefore, increase the understanding and intervention perspectives related to these processes. (AU)
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