Cost-benefit ratio of the immunoregulatory action of the splanchnic nerve: the case of a bacterial infection following a viral challenge

• Grant number: 24/22378-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2025
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alexandre Alarcon Steiner
• Grantee: Mariana Mayumi Teramoto
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The inflammatory response to a widespread infection is an immune response mechanism capable of protecting the body against pathogen infections, but if unregulated, it can also lead to sepsis. The inflammatory reflex pathway has been described as capable of generating the necessary regulation for the acute inflammatory response.The increased predisposition to bacterial infections due to viral infections is an alarming clinical issue that increases the morbidity and mortality of at-risk patients. Therefore, it is important to understand how immunomodulation can impact this context. The study of the role of the neuroimmune axis in the inflammatory reflex pathway has shown great significance, with the parasympathetic innervation having it's role in this pathway better clarified than the sympathetic innervation. Thus, it is relevant to investigate the role of sympathetic pathways in this clinical picture. Previous studies in the laboratory have revealed that bilateral splanchnicectomy associated with E. coli infection can result in a more pronounced inflammatory response, revealing that the greater splanchnic nerve, part of the sympathetic innervation, acts in the inflammatory reflex pathway, attenuating the inflammatory response. Taking this discovery into account, we seek to understand whether the greater splanchnic nerve plays a role in a scenario involving multiple sequential infections.Thus, this project aims to obtain a greater understanding of the role of this nerve in increased susceptibility to co-infections or secondary bacterial infections following viral infections, a clinically significant context. In order to study the immunoregulatory role in this scenario, mice will be subjected to infection by the viral mimetic poly I:C and subsequent infections by E. coli, allowing an analysis of the role of the greater splanchnic nerve through bilateral splanchnicectomy or sham procedure, at different points in this scenario.Following this, the bacterial load will be assessed in the spleen, lungs and peritoneum, along with the evaluation of peritoneal neutrophil secretion proteins (BPI and S100A9) and blood secretion of adrenaline and noradrenaline.