Loss of the mammalian G-protein coupled receptor, G2A, modulates severity of invasive pulmonary aspergillosis

• DOI: 10.3389/fimmu.2023.1173544
• Publication Date: 2023-06-26T10:24:19Z
• Authors: Breanne N. Steffan; Dante Calise; Sung Chul Park; Mengyao Niu; Jun Yang; Bruce D. Hammock; MaryJane Jones; Chad Steele; Nancy P. Keller
• Keywords: Oxylipin; C-type lectin

Background Aspergillus fumigatus is a well-known opportunistic pathogen that causes range of diseases including the often-fatal disease, invasive pulmonary aspergillosis (IPA), in immunocompromised populations. The severity IPA dependent on both host- and pathogen-derived signaling molecules mediate host immunity fungal growth. Oxylipins are bioactive oxygenated fatty acids known to influence immune response developmental programs. synthesizes 8-HODE 5,8-diHODE have structural similarities 9-HODE 13-HODE, which ligands G-protein-coupled receptor G2A (GPR132). Materials methods were extracted from infected lung tissue assess oxylipin production Pathhunter β-arrestin assay was used agonist antagonist activity by oxylipins G2A. An immunocompetent model A. infection changes survival responses for G2A-/- mice. Results Here we report produced mice vitro ligand assays suggest partial antagonist. To address hypothesis could be involved progression IPA, assessed infection. showed advantage over wild-type mice; this accompanied increased recruitment neutrophils levels inflammatory markers -infected lungs. Conclusions We conclude suppresses although it remains unclear if activities.