Akt1 Signaling in dendritic cells modulates host-microbial interaction and inflammatory bone resorption

Author(s)

Adriana Alicia Cabrera Ortega

• Document type: Doctoral Thesis
• Press: Araraquara. 2018-05-18.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Odontologia. Araraquara
• Defense date: 2018-03-26
• Advisor: Morgana Rodrigues Guimarães Stabili

Abstract

Dendritic cells play a crucial role in the pathogenesis of periodontal diseases by orchestrating the adaptive immune response and their role as osteoclasts precursors. Akt signaling plays an important role in processes such as metabolism, proliferation, apoptosis and also in the immune response. Evidence indicates that Akt1 plays a role of negative endogenous regulator of the inflammatory response; but can both stimulate and inhibit osteoclastogenesis. Considering that dendritic cells participate in both inflammation/immune response and turnover of bone tissue as osteoclast precursor cells, we have proposed to evaluate in a vivo study the role of Akt1 activity in inflammation associated with microbiota-host interactions, as well as to evaluate in vitro the role of the Akt1 signaling pathway in dendritic cell biology. In vivo study was employed a model of experimental periodontal disease induced by P. gingivalis and Fusobacterium nucleatum in transgenic animals model with conditional gene deletion. The outcomes evaluated were: inflammation (morphometry), bone resorption (μCT), osteoclastogenesis (IHC), antibodies specific for P.gingivalis and Fusobacterium nucleatum (ELISA). In vitro study was evaluated the role of Akt1 signaling pathway on the following outcomes related to dendritic cell biology: proliferation, apoptosis, phagocytic activity, migration, antigen presentation and osteoclastogenesis The results showed that signaling via Akt1 in dendritic cells seems to play an important role in the pathogenesis of periodontal disease, modifying the intensity of the adaptive immune response as well as its capacity in osteoclastic differentiation, thus modifying the physiological turnover of the alveolar bone. Futhermore, it is possible to conclude that Akt signaling is necessary for the development of biological functions (proliferation, phagocytosis, antigen presentation and osteoclast differentiation) of dendritic cells. (AU)

• FAPESP's process: 15/10100-8 - Akt1 signaling in dendritic cells modulates host-microbe interactions and inflammatory bone resorption
• Grantee: Adriana Alícia Cabrera Ortega
• Support Opportunities: Scholarships in Brazil - Doctorate