{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T20:44:37Z","timestamp":1775940277824,"version":"3.50.1"},"posted":{"date-parts":[[2025,3,11]]},"group-title":"Immunology","reference-count":80,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,11]]},"abstract":"<jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>\n                    The miR-183\/96\/182 cluster (miR-183C) is required for normal functions of sensory neurons (SN) and various immune cells, including myeloid cells (MC). This research aims to reveal the roles of miR-183C of SN in the interplay of corneal sensory nerves (CSN) and MC during\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    (PA) keratitis.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Double-tracing mice with SN-specific (SNS) conditional knockout of miR-183C (CKO) and age-and sex-matched wild type (WT) controls were used. Their CSN are labeled with Red Fluorescent Protein (RFP); MC with Enhanced Green (EG)FP. The left corneas were scarified and infected with ATCC19660 PA. Corneal flatmounts were prepared at 3, 6, and 12 hours post-infection (hpi) and 1, 3, and 5 days (d)pi for confocal microscopy. Myeloperoxidase (MPO) assay and plate count were performed at 1 dpi.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In WT mice, CSN began to degenerate as early as 3 hpi, starting from the fine terminal CSN in the epithelial\/subepithelial layers, most prominently in the central region. By 1 dpi, CSN in the epithelium\/subepithelial layer were nearly completely destroyed, while stromal nerves persisted. From 3 dpi, CSN were obliterated in both layers. In CKO vs WT mice, CNS followed a slightly slower pace of degeneration. CSN density was decreased at 3 and 6 hpi. However, at 3 dpi, residual large-diameter stromal CSN were better preserved. MC were decreased in the central cornea at 3 and 6 hpi, but increased in the periphery. Both changes were more prominent in CKO vs WT mice. At 12 hpi, densely packed MC formed a ring-shaped band circling a \u201cdark\u201d zone nearly devoid of MC, colocalizing with CSN most degenerated zone in the central cornea. In CKO vs WT, the ring center was larger with fewer MC. At 1 dpi, the entire cornea was filled with MC; however, MC density was lower in CKO mice. An MPO assay showed decreased neutrophils in PA-infected cornea of CKO mice. This led to a decreased severity of PA keratitis at 3 dpi.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This double-tracing model reveals the interplay between CSN and MC during PA keratitis with greater clarity, providing new insights into PA keratitis. CSN-imposed modulation on innate immunity is most impressive within 24 hours after infection. Functionally, the miR-183C in CSN modulates CSN density and the dynamics of MC fluxes-a neuroimmune interaction in display.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.03.06.641908","type":"posted-content","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T12:50:50Z","timestamp":1741870250000},"source":"Crossref","is-referenced-by-count":0,"title":["New Insight Into the Neuroimmune Interplay In\n                  <i>Pseudomonas aeruginosa<\/i>\n                  Keratitis"],"prefix":"10.64898","author":[{"given":"Naman","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine\/Kresge Eye Institute, Detroit, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"LoGrasso","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine\/Kresge Eye Institute, Detroit, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda D.","family":"Hazlett","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine\/Kresge Eye Institute, Detroit, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6140-0943","authenticated-orcid":false,"given":"Shunbin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine\/Kresge Eye Institute, Detroit, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041113045945000_2025.03.06.641908v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2003.10.002"},{"key":"2026041113045945000_2025.03.06.641908v1.2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.2008\/003723-0"},{"key":"2026041113045945000_2025.03.06.641908v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/eye.2011.288"},{"key":"2026041113045945000_2025.03.06.641908v1.4","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e318156caf2"},{"key":"2026041113045945000_2025.03.06.641908v1.5","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-4593"},{"key":"2026041113045945000_2025.03.06.641908v1.6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000826"},{"key":"2026041113045945000_2025.03.06.641908v1.7","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1995.01100100045026"},{"key":"2026041113045945000_2025.03.06.641908v1.8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2007.01681.x"},{"key":"2026041113045945000_2025.03.06.641908v1.9","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.19.232660"},{"key":"2026041113045945000_2025.03.06.641908v1.10","unstructured":"Chodosh J . 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