BackgroundAspergillus fumigatusis 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 andAspergillusdevelopmental programs.Aspergillussynthesizes 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).Materials and methodsOxylipins were extracted from infected lung tissue to assess fungal oxylipin production and the Pathhunter β-arrestin assay was used to assess agonist and antagonist activity by fungal oxylipins on G2A. An immunocompetent model ofA. fumigatusinfection was used to assess changes in survival and immune responses for G2A-/- mice.ResultsHere we report thatAspergillusoxylipins are produced in lung tissue of infected mice andin vitroligand 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 toA. fumigatusinfection. 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 inA. fumigatus-infected lungs.ConclusionsWe conclude that G2A suppresses host inflammatory responses toAspergillus fumigatusalthough it remains unclear if fungal oxylipins are involved in G2A activities.