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However, in the last years, pneumonia caused by the opportunistic pathogen <jats:italic>Acinetobacter baumannii<\/jats:italic> have become difficult to treat due to the increase of the number of extensively drug resistant strains. In this study, we report for the first time the use of an <jats:italic>ex vivo<\/jats:italic> air\u2013liquid interface (ALI) model of differentiated human bronchial epithelial cells to unravel the early response to <jats:italic>A. baumannii<\/jats:italic> infection.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Epithelial integrity, tissue architecture, and goblet cell function were assessed through FITC-dextran permeability assays, hematoxylin and eosin staining, and indirect immunofluorescence. Transcriptomic profiling was performed to characterize host gene expression changes. <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Initial tissue damage began as early as at 4\u00a0h post-infection (hpi); at 24\u00a0hpi, goblet cell hypertrophy, reduced mucin secretion, and compromised epithelial integrity were highly evident. Transcriptomic data at 4\u00a0hpi revealed 668 differentially expressed genes (441 upregulated, 227 downregulated), mainly involved in a strong pro-inflammatory response and characterized by IL-8\/CCL20-driven neutrophil recruitment and type 2 cytokine activation (IL-4, IL-13). Noteworthy, genes related to cytoskeletal organization, adhesion, and extracellular matrix remodeling were significantly altered, suggesting a bacterial mechanism to enhanced tissue dissemination. The PI3K-Akt survival pathway was inhibited, with downregulation of <jats:italic>PIK3R1<\/jats:italic> and <jats:italic>PIK3R2<\/jats:italic> genes, implying the induction of apoptosis\/cell death and epithelial damage. Our findings are in agreement with previous <jats:italic>in vivo<\/jats:italic> studies, further strengthening the value of our ALI model in mimicking the early infection response of bronchial cells to <jats:italic>A. baumannii<\/jats:italic> infection.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Our data highlight the early molecular mechanisms underlying <jats:italic>A. baumannii<\/jats:italic> pathogenesis and open new avenues for future investigations for therapeutic interventions.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphical Abstract<\/jats:title>\n          <\/jats:sec>","DOI":"10.1186\/s12929-025-01159-1","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T08:38:59Z","timestamp":1752136739000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Goblet cell breakdown: transcriptomics reveals Acinetobacter baumannii early and robust inflammatory response in differentiated human bronchial epithelial cells"],"prefix":"10.1186","volume":"32","author":[{"given":"Daniela","family":"Scribano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Tito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astri D.","family":"Tagueha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Pasqua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"De Angelis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Fazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolores","family":"Limongi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"De Angelis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Nencioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Teresa","family":"Palamara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2163-1613","authenticated-orcid":false,"given":"Cecilia","family":"Ambrosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"issue":"8","key":"1159_CR1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011520","volume":"19","author":"AK Cain","year":"2023","unstructured":"Cain AK, Hamidian M. 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