Participation of NOD1, NOD2 and Ripk2 in the exacerbation of allergic airway disease associated to obesity

• Grant number: 21/09365-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: February 01, 2022
• End date: January 31, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Gabriel Forato Anhê
• Grantee: Rodrigo Rodrigues e Lacerda
• Supervisor: Jonathan Schertzer
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: McMaster University, Canada
• Associated to the scholarship: 19/03751-3 - Influence of the history of Obesity originated at different moments of life in allergic pulmonary inflammation, BP.PD

Abstract

We and others have demonstrated that obese mice subjected to the model of sensitization and challenge with ovalbumin (OVA) display increased lung eosinophil infiltration and elevated production of TH2 cytokines when compared to lean littermates. Apart of these consistent studies, it still remains to be described the precise mechanism by which obesity is linked to asthma exacerbation. Pattern recognition receptors (PRRs) along with gut dysbiosis have been consistently implicated in several metabolic adaptations to obesity. The present proposal aims to elucidate if intracellular nucleotide-binding oligomerization domain (NOD) receptor NOD1 and NOD2 and their downstream adaptor RIPK2 play a role in the exacerbated allergic airway disease seen in obese mice. To achieve this goal, female wild-type C57BL/6J, Ripk2/, Nod2/ and Nod1/ mice will be fed either with standard chow or HFD for 8 weeks. Sensitization and challenge with OVA will be performed during the 7th and the 8th weeks of diet. Serum IgE, total and differential leukocyte counts in lung and BAL, collagen / elastic / mucus production, and Th1 and Th2 cytokine production / expression in BAL, airway and lung will be assessed as readouts of allergic airway disease. Our project will also determine if the expression of Ripk2, NOD2 and NOD1 in hematopoietic cells are necessary for the exacerbated allergic airway disease in HFD-mice. This aim will be achieved by transplanting bone marrow cells from Ripk2/, Nod2/ and Nod1/ mice in to C57BL/6J mice. After transplantation, chimeric recipient mice will be fed with HFD and subjected to the sensitization/challenge with OVA protocol. The above-mentioned end points of allergic airway disease will be also assessed in the recipient mice. (AU)