Molecular mechanisms underlying the resistance to the immunosupression development in neonatal sepsis

• Grant number: 17/10255-7
• Support Opportunities: Research Grants - Visiting Researcher Grant - International
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Fernando de Queiroz Cunha
• Grantee: Fernando de Queiroz Cunha
• Visiting researcher: Foo Yew Liew
• Visiting researcher institution: University of Glasgow, Scotland
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

Sepsis is a major cause of mortality in hospitalized patients worldwide. Medically is defined as Systemic Inflammatory Response Syndrome (SIRS) resulting from an infectious process, which commonly, can develop into a multiple organ dysfunction followed by death. It is noteworthy that sepsis mortality rate in pediatric patients is significantly higher than in adults. In addition to the severity of sepsis, adult individuals surviving severe sepsis develop a long-term immunosuppression, characterized by increased mortality from secondary infections or other diseases, which may last for up to five years. Surprisingly, preliminary data from our research group demonstrated that neonatal animals surviving severe sepsis, although more susceptible to acute phase of sepsis presenting higher mortality rates, do not develop the immunosuppression, suggesting that immune dysfunction induced by severe sepsis may be an event dependent of age. Nevertheless, the mechanisms involved in the relationship of this biological phenomenon with age is still unknown. In this context, our group recently demonstrated that cytokines type 2 (IL-4, IL-10 and IL-33) and increased frequency of Tregs cells mediated by M2 profile Macrophages play a central role in immunosuppression induced by severe sepsis in adults. However, until the present there are no studies analyzing the profile of type 2 cytokines, M2 macrophages and Treg cells in animals or pediatric patient survivors to severe sepsis. Thus, the aim of this project is to characterize the axis M2 macrophages/cytokines type 2/Tregs, and perform comparative study of epigenetic-molecular events involved in the differentiation of Tregs in neonates and adult individuals surviving sepsis. This study may contribute to the understanding of mechanisms related to the development of immunosuppression induced by sepsis and contribute to the formation knowledge that will enable future therapeutic interventions. (AU)