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Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>Aspergillus fumigatus<\/jats:italic> is a well-known opportunistic pathogen that causes a range of diseases including the often-fatal disease, invasive pulmonary aspergillosis (IPA), in immunocompromised populations. The severity of IPA is dependent on both host- and pathogen-derived signaling molecules that mediate host immunity and fungal growth. Oxylipins are bioactive oxygenated fatty acids known to influence host immune response and <jats:italic>Aspergillus<\/jats:italic> developmental programs. <jats:italic>Aspergillus<\/jats:italic> synthesizes 8-HODE and 5,8-diHODE that have structural similarities to 9-HODE and 13-HODE, which are known ligands of the host G-protein-coupled receptor G2A (GPR132).<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Oxylipins were extracted from infected lung tissue to assess fungal oxylipin production and the Pathhunter \u03b2-arrestin assay was used to assess agonist and antagonist activity by fungal oxylipins on G2A. An immunocompetent model of <jats:italic>A. fumigatus<\/jats:italic> infection was used to assess changes in survival and immune responses for G2A-\/- mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here we report that <jats:italic>Aspergillus<\/jats:italic> oxylipins are produced in lung tissue of infected mice and <jats:italic>in vitro<\/jats:italic> ligand assays suggest 8-HODE is a G2A agonist and 5,8-diHODE is a partial antagonist. To address the hypothesis that G2A could be involved in the progression of IPA, we assessed the response of G2A-\/- mice to <jats:italic>A. fumigatus<\/jats:italic> infection. G2A-\/- mice showed a survival advantage over wild-type mice; this was accompanied by increased recruitment of G2A-\/- neutrophils and increased levels of inflammatory markers in <jats:italic>A. fumigatus<\/jats:italic>-infected lungs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We conclude that G2A suppresses host inflammatory responses to <jats:italic>Aspergillus fumigatus<\/jats:italic> although it remains unclear if fungal oxylipins are involved in G2A activities.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1173544","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T10:24:19Z","timestamp":1687775059000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Loss of the mammalian G-protein coupled receptor, G2A, modulates severity of invasive pulmonary aspergillosis"],"prefix":"10.3389","volume":"14","author":[{"given":"Breanne 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