Integrative metabolomics and transcriptomics identifies itaconate as an adjunct therapy to treat ocular bacterial infection.

ABSTRACT: The eye is highly susceptible to inflammation-mediated tissue damage evoked during bacterial infection. However, mechanisms regulating inflammation to protect the eye remain elusive. Here, we used integrated metabolomics and transcriptomics to show that the immunomodulatory metabolite itaconate and immune-responsive gene 1 (Irg1) are induced in bacterial (Staphylococcus aureus)-infected mouse eyes, bone-marrow-derived macrophages (BMDMs), and Müller glia. Itaconate levels are also elevated in the vitreous of patients with bacterial endophthalmitis. Irg1 deficiency in mice led to increased ocular pathology. Conversely, intraocular administration of itaconate protects both Irg1^-/- and wild-type mice from bacterial endophthalmitis by reducing infl

SUBMITTER: Singh S 

PROVIDER: S-EPMC8149370 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature