Influence of microbiota on the role of macrophages during acute renal injury induced by cisplatin in zebrafish

Abstract

Kidneys are the organs responsible for managing a set of physiological tasks that maintain the body's homeostasis, such as the removal of toxic metabolites from the blood, production of hormones and the regulation of electrolyte balance. Kidney lesions are responsible for a high number of deaths in hospitals and are due to several sources, which depending on severity can lead to a rapid loss of organ functions in hours or days, causing what is known as acute kidney injury (AKI). During the injury process, the immune system acts in a way, often, harmful to the organ. Due to the death of renal cells and the release of inflammatory signals, cells of the immune system, such as monocytes and neutrophils, are recruited to generate a cellular infiltrate capable of aggravating the lesion, thus accelerating loss of function. One of the main cells involved in this process are macrophages, which participate in the first phase of the disease differentiated into their M1 profile, classically described as proinflammatory, and also during the tissue recovery phase, differentiated in M2 helping tissue repair. On the other hand, the literature has demonstrated that products derived from the metabolism of bacteria belonging to the intestinal microbiota are capable of modulating the immune response in a LRA process, but the influence of these products and, even of the microbiota, on the function, migration and differentiation of Macrophages has not been well described. In recent years, the use of zebrafish as a model of study has gained importance due to the capacity of renal regeneration, allowing a deeper understanding of the mechanisms of tissue recovery and resolution of the lesion. Therefore, the hypothesis of our project is that the microbiota influences the function / migration of macrophages during the repair process of AKI in adult zebrafish. To answer this hypothesis, we will work with a model of cisplatin-induced renal injury and characterize macrophages from immunohistochemistry and immunofluorescence imaging and inflammatory and anti-inflammatory markers.We hope to demonstrate that zebrafish is an accessible model for studying LRA and to characterize the subtypes of macrophages that are deleterious in renal injury. (AU)