{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T04:12:47Z","timestamp":1793679167248,"version":"4.5.1"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"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>Introduction<\/jats:title><jats:p>Cochlear injury activates the resident macrophages (RM) and recruits the blood-circulating monocytes and monocyte-derived macrophages (Mo\/Mo-M), but their specific functions in the injured cochlea are unknown. It is well-established that the chemokine fractalkine receptor (CX<jats:sub>3<\/jats:sub>CR1), expressed by cochlear macrophages, influences the density of those macrophages and promotes synaptic repair and spiral ganglion neuron (SGN) survival in the injured cochlea. As CX<jats:sub>3<\/jats:sub>CR1 is expressed on both RM and Mo\/Mo-M, it remains unclear if CX<jats:sub>3<\/jats:sub>CR1- expressing RM and Mo\/Mo-M are distinct and differentially promote SGN survival after cochlear injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used a fate mapping tamoxifen-inducible CX<jats:sub>3<\/jats:sub>CR1 mouse model (CX<jats:sub>3<\/jats:sub>CR1<jats:sup>YFP\u2212CreERT2\/wildtype<\/jats:sup>:R26<jats:sup>RFP<\/jats:sup>) wherein CX<jats:sub>3<\/jats:sub>CR1-expressing RM and Mo\/Mo-M are endogenously labeled with different fluorescent reporters. Tamoxifen injections were performed intraperitoneally at 4 weeks of age, and recombination efficiency was evaluated after 2 and 60 days. Mice were subjected to an acoustic trauma of 112 decibel (dB) sound pressure level (SPL) at 8\u201316-kHz octave band, for 2 hours. Heterogeneity in cochlear macrophages was defined with respect to their origin, turnover, spatiotemporal distribution, morphology, and fate following acoustic trauma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After 60 days of tamoxifen injections at 4 weeks of age, long-lived cochlear RM were YFP+ RFP+ with 98.0% \u00b1 1.7% recombinant efficiency, and short-lived blood-circulating CX<jats:sub>3<\/jats:sub>CR1 lineage (Mo\/Mo-M) cells were YFP+ RFP\u2212 with 2.5% \u00b1 1.1% recombinant efficiency. Following an acoustic trauma, morphologically similar RM and Mo\/Mo-M were observed in the spiral ganglion, lamina, and ligament and around the sensory epithelium. The quantification of RM and Mo\/Mo-M in the spiral lamina and ganglion revealed distinct spatial and temporal distribution patterns. Furthermore, recruited Mo\/Mo-M expressed classical monocyte markers such as Ly6C and CCR2. Both RM and Mo\/Mo-M were positive for proliferation marker, Ki67, and negative for apoptotic marker, cleaved caspase-3, suggesting that the overall increase in macrophage numbers in the noise-injured cochlea is a contribution of both the proliferation of RM and the recruitment of Mo\/Mo-M. Probing for blood-clotting protein, fibrinogen, showed its presence in the cochlea after acoustic trauma, suggesting vascular damage that positively and strongly correlated with the time course of the recruitment of blood-circulating Mo\/Mo-M in the noise-injured cochlea.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These data imply that macrophages in the noise-injured cochlea are heterogeneous regarding their ontogeny, distribution, and fate. They offer a robust tool to study the precise roles of resident and recruited macrophages in healthy and pathological ears.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1678176","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T13:16:47Z","timestamp":1758287807000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["CX3CR1 fate mapping in vivo distinguishes cochlear resident and recruited macrophages after acoustic trauma"],"prefix":"10.3389","volume":"16","author":[{"given":"Sree Varshini","family":"Murali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew 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