Intervention in signaling pathways associated with the recognition of cellular damage to reduce the pathology of severe forms of malaria and tuberculosis

Abstract

The dead cells as a result of the tissue damage are rapidly phagocytosed, but before they disappear, they alert the surrounding cells to activate the repair programs. The recognition by the innate immune system of cellular damage contributes to the development of inflammatory processes and tissue repair immune responses, but can also determine the worsening of the lesions in the damaged tissues. In some cases, uncontrolled cell death can trigger a destructive cascade process that ends up amplifying the tissue lesions and worsening the prognosis of the disease. The general objective of this project is to characterize the cellular damage signal receptors that are involved in the progression of the serious forms of experimental malaria and tuberculosis, in order to interfere in these signaling pathways in order to improve the prognosis of the diseases. These infectious diseases are among the most prevalent in the human species, accounting jointly for more than 1 million deaths annually worldwide. It is also intended to evaluate the importance of signs of damage in the development of the immune response acquired during these infectious diseases. This study may provide an essential knowledge for the development of new therapeutic approaches that can be applied, together with those already used, in the treatment of severe forms of malaria and tuberculosis, as well as other infectious or non-infectious diseases characterized by tissue damage Extensive. In addition, this study can unravel new molecular mechanisms involved in the recognition of cellular damage and, consequently, broaden the understanding and intervention perspectives related to these processes.