{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T17:06:38Z","timestamp":1770138398594,"version":"3.49.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007509","name":"Sociedad Espa\u00f1ola de Neumolog\u00eda y Cirug\u00eda Tor\u00e1cica","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007509","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013347","name":"European Society of Intensive Care Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Hypercapnic acidosis (HCA) is a hallmark of acute hypercapnic respiratory failure, often triggered by respiratory infections. Its role in lung injury remains controversial, with both protective and detrimental effects reported. However, the specific impact on pulmonary immune responses to lung infections remain poorly understood. To investigate the impact of HCA on alveolar response during infection, we developed an\n                      <jats:italic>in vitro<\/jats:italic>\n                      model combining human alveolar epithelial cells (type I and II) and macrophage-like THP-1 cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The co-culture and monocultures were infected with\n                      <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                      or\n                      <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                      under normocapnic or HCA conditions. At 1 hour and 24 hours post-infection, we assessed inflammatory cytokine expression (IL-1\u03b2, CCL2, IL-8), tight junction protein levels (occludin, ZO-1) and bacterial survival.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HCA modulated inflammation in pathogen-specific manner: IL-1\u03b2 induction by\n                      <jats:italic>S. pneumoniae<\/jats:italic>\n                      was mainly CO\n                      <jats:sub>2<\/jats:sub>\n                      -driven, while\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      triggered strong IL-1\u03b2 regardless of CO\n                      <jats:sub>2<\/jats:sub>\n                      . Tight junction proteins were upregulated at 1 hour under HCA, particularly with macrophages, but occludin declined at 24 hours, potentially impairing epithelial repair. While extracellular bacterial loads were unaffected by CO\n                      <jats:sub>2<\/jats:sub>\n                      , HCA promoted intracellular replication of\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      in macrophages, without affecting intracellular survival in epithelial cells or overall bacterial burden in\n                      <jats:italic>S. pneumoniae<\/jats:italic>\n                      -infected cultures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HCA condition differentially influence host responses depending on the infectious pathogen, compromising the barrier function and prolonging lung inflammation with differences according to time culture, which could benefit bacterial persistence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1708427","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T06:29:11Z","timestamp":1770100151000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Hypercapnic acidosis affects in vitro lung infection response in a pathogen-specific manner"],"prefix":"10.3389","volume":"15","author":[{"given":"Elena","family":"Campa\u00f1a-Duel","sequence":"first","affiliation":[{"name":"Critical Care Research Center, Parc Taul\u00ed Hospital Universitari, Institut d\u2019Investigaci\u00f3 i Innovaci\u00f3 Parc Taul\u00ed (I3PT-CERCA) and Universitat Aut\u00f2noma de Barcelona","place":["Sabadell, Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica En Red de Enfermedades Respiratorias, Instituto de Salud Carlos III","place":["Barcelona, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aina","family":"Areny-Balaguer\u00f3","sequence":"additional","affiliation":[{"name":"Critical Care Research Center, Parc Taul\u00ed Hospital Universitari, Institut d\u2019Investigaci\u00f3 i Innovaci\u00f3 Parc Taul\u00ed (I3PT-CERCA) and Universitat Aut\u00f2noma de Barcelona","place":["Sabadell, Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica En Red de Enfermedades Respiratorias, Instituto de Salud Carlos III","place":["Barcelona, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Morales-Quinteros","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica En Red de Enfermedades Respiratorias, Instituto de Salud Carlos III","place":["Barcelona, Spain"]},{"name":"Servei de Medicina Intensiva, Hospital Universitari Vall d\u2019Hebron - 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