Influence of nitric oxide in the immune response mediated by activation of Toll-like receptors in mice

• Grant number: 12/24033-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2013
• End date: June 30, 2015
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Cyro Alves de Brito
• Grantee: Beatriz de Stefano Shida
• Host Institution: Instituto Adolfo Lutz (IAL). Coordenadoria de Controle de Doenças (CCD). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The neonatal period is generally marked by an inability to generate effective immune responses, which lead to susceptibility to bacterial and viral infections. This relative immaturity is related to the lack of memory cells and decreased ability to develop adequate innate and adaptive immune responses. Moreover, murine newborns preferentially develop a Th2 response that appears to be caused by low secretion of Th1 cytokines such as interferon-gamma and its inducer, IL-12.In the last years, the role of innate immunity in the development of an effective immune response, directing the response pattern (eg, Th1, Th2, Th17) and immune tolerance has been extensively studied. Cytokine production and expression of membrane molecules by cells such as macrophages, dendritic cells and NK cells are important for establishment of the adaptive immune response. The use of TLR agonist compounds must be a promising strategy in modulating the immune response and as an adjuvant in vaccines, especially in the early stages of life, when the immune system is immature. However, results from our group suggest that CpG, a TLR9 agonist, has a less modulating effect in neonates than adults when analyzing the production of antibodies and cytokines. Also, nitric oxide, by its diverse effects on the immune system, can exert important regulatory functions in the neonatal immune response. It is possible that pro-inflammatory stimuli, such stimuli by agonists of TLRs, activate immunosuppressive mechanisms in neonates. The possible involvement of nitric oxide in modulating the production of cytokines and chemokines in neonatal mice is not clear and is of great interest in understanding the regulation of immunity in this lifetime. This project will contribute to a better understanding of the functioning of the immune system of neonates compared with the stimulation of innate immunity, seeing a big difference to the adult immune system. The advances in knowledge about the action of agonists of Toll-like receptors in the neonatal immune system will also contribute to the study and application of these agonists as adjuvants in vaccines, treatment of diseases, and strategies to modulate allergic responses.(AU)