{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T03:03:27Z","timestamp":1785294207861,"version":"3.55.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:00:00Z","timestamp":1729036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>The aim of this study was to investigate whether Dectin-1 influences the immune-inflammatory response in <jats:italic>A. fumigatus<\/jats:italic> keratitis by modulating macrophage polarization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>1. The models of 1-day, 3-day, and 5-day of fungal keratitis were established in SPF C57BL\/6 mice after stimulation by <jats:italic>A. fumigatus.<\/jats:italic> Dectin-1 agonist (curdlan) and antagonist (laminaran) were injected separately in the mouse subconjunctivae for 1 day in the established mouse model of <jats:italic>A. fumigatus<\/jats:italic> keratitis; PBS was used as the control. Inflammation of the mouse cornea was observed under a slit lamp to obtain a clinical score. 2. The expression of M1 (TNF-\u03b1, INOS, IL-6, IL-12) and M2 (Arg-1, IL-10, Fizz-1, Ym-1) cytokine-encoding mRNAs was quantified by RT-PCR. 3. Changes in the number of macrophages and expression of M1 and M2 macrophages in mouse corneas detected by immunofluorescence and flow cytometry. 4. Pre-treatment of RAW264.7 cells with MAPK cell signaling pathway inhibitors SB203580 (p38 inhibitor, 10\u00b5M), U0126 (ERK inhibitor, 20\u00b5M), SP600125 (JNK inhibitor, 10\u00b5M) and DMSO separately for 2\u00a0h, and stimulated by <jats:italic>A. fumigatus<\/jats:italic> for 12\u00a0h. Changes in the mRNA expression of M1 and M2 cytokines in the macrophages were quantified by RT-PCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>1. With curdlan pre-treatment, mouse corneal inflammation worsened, and the clinical score increased after infection. In contrast, in the laminaran pre-treated group, corneal inflammation was alleviated and the clinical score decreased significantly compared to the PBS group after infection. 2. Compared with the control group, the expression levels of macrophage phenotype-related M1 and M2 cytokine mRNAs increased significantly 1, 3, and 5 days after <jats:italic>A. fumigatus<\/jats:italic> infected the corneas of mice. 3. With curdlan pre-treatment, the expression of mRNAs encoding M1 cytokines increased, while those encoding M2 cytokines decreased in the cornea compared to the PBS group. In contrast, after infection, mRNA levels for M1 cytokines decreased significantly and those for M2 cytokines increased in the cornea of the laminaran pre-treated group compared to the PBS group. 4. The number of macrophages in the corneal stroma of mice in the curdlan pretreatment group increased significantly compared with the PBS group, while in the laminaran pretreatment group this number decreased significantly. 5. The results of flow cytometry showed that after 3 days of mouse corneal <jats:italic>A. fumigatus<\/jats:italic> infection, the number of macrophages in the mouse <jats:italic>A. fumigatus<\/jats:italic> model in the curdlan pretreatment group was increased (10.4%) and the number of macrophages in the mouse <jats:italic>A. fumigatus<\/jats:italic> model in the laminaran pretreatment group (6.31%), when compared with the AF+FBS group (7.91%). The proportion of M1-type macrophages was increased in the curdlan pretreated group (55.6%) compared to the AF+FBS group (51.2%), the proportion of laminaran pretreatment group had a decreased proportion of M1-type macrophages (46.8%); while M2-type macrophages were the opposite of M1-type: the proportion of M2-type macrophages was 49.2% in the AF+FBS group, the proportion of M2-type macrophages was decreased in the curdlan pretreatment group (44.0%), and the proportion of M2-type macrophages was increased in the laminaran pretreatment group (53.5%). 6. Expression of M1 and M2 cytokine-encoding mRNAs decreased and increased, respectively, after infection, in the RAW264.7 cells pre-treated with MAPK pathway inhibitors, compared to the control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In a mouse model of <jats:italic>A. fumigatus<\/jats:italic> keratitis, Dectin-1 can affect macrophage recruitment and polarization, may regulate macrophage phenotype-associated factor changes through the MAPK signaling pathway.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1431633","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T12:15:30Z","timestamp":1729080930000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Dectin-1 participates in the immune-inflammatory response to mouse Aspergillus fumigatus keratitis by modulating macrophage polarization"],"prefix":"10.3389","volume":"15","author":[{"given":"Liu","family":"Guibo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Chunxu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Biao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Zhaolei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Wenwen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Xiangnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wentao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Hongmin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yonghua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Guoqiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1093\/mmy\/myx125","article-title":"A novel, tomographic imaging probe for rapid diagnosis of fungal keratitis","volume":"56","author":"Lee","year":"2018","journal-title":"Med Mycol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.18240\/ijo.2021.07.20","article-title":"Immunologic mechanism of fungal keratitis","volume":"14","author":"Yang","year":"2021","journal-title":"Int J Ophthalmol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1159\/000513582","article-title":"Novel strategies to target mast cells in disease","volume":"13","author":"Paivandy","year":"2021","journal-title":"J Innate Immun"},{"key":"B4","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1167\/iovs.62.6.10","article-title":"Role of IL-36\u03b3\/IL-36R signaling in corneal innate defense against candida albicans keratitis","volume":"62","author":"Dai","year":"2021","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-018-1859-4","article-title":"Fusarium solani activates dectin-1 in experimentally induced keratomycosis","volume":"38","author":"Xu","year":"2018","journal-title":"Curr Med Sci"},{"key":"B6","doi-asserted-by":"publisher","first-page":"3194","DOI":"10.3390\/vaccines8020303","article-title":"Innate immune receptors and defense against primary pathogenic fungi","volume":"8","author":"Kirkland","year":"2020","journal-title":"Vaccines (Basel)"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01182","article-title":"Protein Deiminase 4 and CR3 Regulate Aspergillus fumigatus and \u03b2-Glucan-Induced Neutrophil Extracellular Trap Formation, but Hyphal Killing Is Dependent Only on CR3","volume":"9","author":"Clark","year":"2018","journal-title":"Front Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s13072-017-0158-9","article-title":"Genome-wide profiling of transcribed enhancers during macrophage activation","volume":"10","author":"Denisenko","year":"2017","journal-title":"Epigenet Chromatin"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.621813","article-title":"Natural polysaccharides and their derivates: A promising natural adjuvant for tumor immunotherapy","volume":"12","author":"Li","year":"2021","journal-title":"Front Pharmacol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-015-1995-y","article-title":"Mol. 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