Transgenerational study of macrophages in the control of infection in low birth weight rats induced by intrauterine malnutrition and its relationship with the intestinal microbiota.

• Grant number: 24/02740-6
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2024
• End date: November 30, 2027
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Richardt Gama Landgraf
• Grantee: Richardt Gama Landgraf
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Associated researchers: Alexandre de Castro Keller ; Maristella de Almeida Vitta Landgraf ; Sandra Andreotti ; Vinicius de Andrade Oliveira
• Associated scholarship(s): 24/23135-3 - Assessment of the Phagocytic and Microbicidal Capacity of Macrophages in Low Birth Weight Rats Induced by Intrauterine Malnutrition, BP.IC

Abstract

In previous work, our group demonstrated that global intrauterine malnutrition led, in 12-week-old Wistar rats, to hypocellularity in the bone marrow and peripheral blood, a reduction in the expression of adhesion molecules and a reduction in the migration of leukocytes in these animals. In this same model, we also observed a reduction in the acute and allergic pulmonary inflammatory response, with lower production of cytokines and lipid mediators and high levels of circulating corticosterone. These data may be related to the greater predisposition to infections presented by individuals with low birth weight. Sepsis is considered a syndrome of systemic inflammatory response to infection, which leads to the death of millions of people worldwide. Its pathophysiology is complex and involves the immunological response and different mechanisms of the inflammatory response, culminating in intense changes in homeostasis in its most advanced stages. advanced. The biochemical cellular changes and basic mechanisms of the inflammatory response in the adult life of first- and second-generation animals that suffered intrauterine malnutrition are poorly studied and understood. It has been demonstrated that the composition and development of the infant intestinal microbiota can be influenced by several prenatal factors, including stress and maternal diet. Furthermore, it can contribute to the development of several chronic diseases in adulthood. Together, these data lead us to question whether, after an infectious stimulus, there would be a change in the composition of the intestinal microbiota concomitantly with a change in the profile of primary, alveolar and peritoneal macrophages, in addition to impairment of the phagocytic and microbicidal capacity of these animals, favoring the establishment of infectious diseases. (AU)