{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:10:10Z","timestamp":1787065810168,"version":"build-2736575974"},"reference-count":50,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T00:00:00Z","timestamp":1634083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY023226"],"award-info":[{"award-number":["R01EY023226"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30EY004068"],"award-info":[{"award-number":["P30EY004068"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["Unrestricted"],"award-info":[{"award-number":["Unrestricted"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Our previous work has shown that topical thymosin beta 4 (T\u03b24) as an adjunct to ciprofloxacin treatment reduces inflammatory mediators and inflammatory cell infiltrates (neutrophils\/PMN and macrophages\/M\u03a6) while enhancing bacterial killing and wound healing pathway activation in an experimental model of P. aeruginosa-induced keratitis. This study aimed to mechanistically examine how T\u03b24 influences M\u03a6 function in particular, leading to reduced inflammation and enhanced host defense following P. aeruginosa-induced infection of the cornea. Flow cytometry was conducted to profile the phenotype of infiltrating M\u03a6 after infection, while generation of reactive nitrogen species and markers of efferocytosis were detected to assess functional activity. In vitro studies were performed utilizing RAW 264.7 cells to verify and extend the in vivo findings. T\u03b24 treatment decreases M\u03a6 infiltration and regulates the activation state in response to infected corneas. M\u03a6 functional data demonstrated that the adjunctive T\u03b24 treatment group significantly downregulated reactive nitrogen species (RNS) production and efferocytotic activity. In addition, the in vitro studies showed that both T\u03b24 alone and adjunctive T\u03b24 treatment influenced M\u03a6 cellular function following LPS stimulation. Collectively, these data provide further evidence that adjunctive T\u03b24 + ciprofloxacin treatment offers a more efficacious option for treating bacterial keratitis. Not only does the adjunctive therapy address both the infectious pathogen and corneal wound healing response, but it also influences M\u03a6 infiltration, activation, and function, as revealed by the current study.<\/jats:p>","DOI":"10.3390\/ijms222011016","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T21:36:15Z","timestamp":1634160975000},"page":"11016","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Adjunctive Thymosin Beta-4 Treatment Influences M\u03a6 Effector Cell Function to Improve Disease Outcome in Pseudomonas aeruginosa-Induced Keratitis"],"prefix":"10.3390","volume":"22","author":[{"given":"Yuxin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Visual & Anatomical Sciences, Wayne State University School of Medicine, 540 E. Canfield Avenue, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W.","family":"Carion","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual & Anatomical Sciences, Wayne State University School of Medicine, 540 E. Canfield Avenue, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul Shukkur","family":"Ebrahim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual & Anatomical Sciences, Wayne State University School of Medicine, 540 E. Canfield Avenue, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4805-7327","authenticated-orcid":false,"given":"Gabriel","family":"Sosne","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual & Anatomical Sciences, Wayne State University School of Medicine, 540 E. Canfield Avenue, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5371-1170","authenticated-orcid":false,"given":"Elizabeth A.","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual & Anatomical Sciences, Wayne State University School of Medicine, 540 E. Canfield Avenue, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.micpath.2016.12.013","article-title":"Pathogenesis of microbial keratitis","volume":"104","author":"Lakhundi","year":"2017","journal-title":"Microb. 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