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However, the anti\u2010inflammatory effect of DI has never been studied in fungal keratitis. In this study, we tested the protective effect of DI against fungal keratitis and assessed the role of NF\u2010E2\u2010related factor\u20102 (Nrf2)\/heme oxygenase\u20101 (HO\u20101) signaling in this process. Eyes of C57BL\/6 (B6) mice were treated with 2\u00a0m\n                    <jats:sc>m<\/jats:sc>\n                    DI after infection with\n                    <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                    . Human corneal epithelial cells (HCECs) were pretreated with 0.25\u00a0m\n                    <jats:sc>m<\/jats:sc>\n                    DI and then incubated with\n                    <jats:italic>A.\u00a0fumigatus<\/jats:italic>\n                    . Clinical scoring, slit\u2010lamp photography, myeloperoxidase determination, flow cytometry and immunostaining were used to assess the disease response and treatment efficacy. PCR, Western blot and ELISA were used to assess the expression of interleukin\u20101\u03b2 (IL\u20101\u03b2), chemokine (C\u2013X\u2013C motif) ligand 1, IL\u20106, IL\u20108, Nrf2 and HO\u20101. In addition, quantification of viable fungi, absorbance assays and fluorimetry were used to measure DI fungistatic activity. We observed that DI\u2010treated eyes showed decreased clinical scores, fungal loads, polymorphonuclear neutrophil (PMN) infiltration and cytokine expression, compared with phosphate\u2010buffered saline\u2010treated infected eyes. DI treatment decreased the cytokine levels in infected corneas and in HCECs stimulated with\n                    <jats:italic>A.\u00a0fumigatus.<\/jats:italic>\n                    Moreover, DI treatment increased Nrf2 and HO\u20101 expression in corneas and nuclear Nrf2 accumulation in HCECs. DI\u2010induced cytokine downregulation was inhibited by pretreatment with an Nrf2 or HO\u20101 inhibitor. Finally, DI treatment reduced the\n                    <jats:italic>A.\u00a0fumigatus<\/jats:italic>\n                    absorbance and fungal mass. These data indicate that DI protects against fungal keratitis by limiting inflammation via the Nrf2\/HO\u20101 signaling pathway and that DI inhibits the growth of\n                    <jats:italic>A.\u00a0fumigatus<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1111\/imcb.12316","type":"journal-article","created":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T09:33:17Z","timestamp":1578907997000},"page":"229-241","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Dimethyl itaconate protects against fungal keratitis by activating the Nrf2\/HO\u20101 signaling pathway"],"prefix":"10.1111","volume":"98","author":[{"given":"Lingwen","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology The Affiliated Hospital of Qingdao University Qingdao 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