Self-nucleic acid sensing in hypersensitivity pneumonitis

• Grant number: 25/10685-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2025
• End date: February 28, 2029
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Nicolas Riteau
• Grantee: Yago Gonçalves de Azevedo
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 25/01171-0 - International Research Center CNRS - USP, AP.CIP

Abstract

Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) characterized by an aberrant immune response to repeated inhaled antigens, leading primarily to T cell-mediated inflammation, granuloma formation, and, in some cases, fibrosis. HP is most commonly associated with exposure to organic dust, mold, bacteria, or bird proteins in occupational or environmental settings, with genetic and environmental factors contributing to its immunopathological response. The molecular pathways of this immune response remain largely unexplored. We hypothesize that inflammation caused by HP-triggering antigens induce tissue damage and cell death with the release of danger signals including host DNA, supported by published data showing high levels of mitochondrial DNA (mDNA) in bronchoalveolar lavage (BAL) and plasma from HP patients as compared to controls. This PhD project aims to investigate the role of nucleic acid sensors, particularly STimulator of INterferon Genes (STING), in HP pathophysiology by 1) developing an experimental model of HP, 2) examining nucleic acid sensing pathways in human samples, and 3) exploring leads identified in human data using the mouse model. A deeper understanding of HP pathophysiology could lead to the discovery of new biomarkers and potential therapeutic targets.