{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T07:32:13Z","timestamp":1793345533738,"version":"4.5.0"},"reference-count":52,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp; Disease"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic airway inflammation can be induced by both chemical and environmental factors. Airway inflammation can be induced through different immune pathways, including allergic Th2\u2010dependent activation of eosinophils and mast cells, Th1\/Th17\u2010dependent neutrophil recruitment, or a combination of both mast cell and neutrophil recruitment, that is extremely difficult to treat. An environmental factor that we have shown to induce neutrophil\u2010mediated lung inflammation is cyanobacterium lipopolysaccharide (LPS). The study has two main objectives: first to determine whether TLR4 is required for cyanobacterium LPS\u2010induced lung inflammation, given our prior findings that it signals differently from other LPS types, and second to test if cyanobacterium LPS exacerbates lung inflammation in a Th2\u2010dependent mouse model of airway hypersensitivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      LPS from the cyanobacterium strain,\n                      <jats:italic>Brasilonema<\/jats:italic>\n                      sp., was purified and used for both in vivo and in vitro assays. For in vitro assays, the TLR4 inhibitor, SPA\u20104, was assessed in its ability to block\n                      <jats:italic>Brasilonema<\/jats:italic>\n                      sp.\u2010dependent IL\u20106 and IL\u20108 induction in lung epithelial cell lines, and in vivo, the ability of\n                      <jats:italic>Brasilonema<\/jats:italic>\n                      sp. LPS to induce lung inflammation was assessed in TLR4\u2010deficient mice in comparison to controls. Finally, Th2\u2010driven lung inflammation was established using ovalbumin and then these mice were exposed to\n                      <jats:italic>Brasilonema<\/jats:italic>\n                      sp. LPS intranasally to assess if\n                      <jats:italic>Brasilonema<\/jats:italic>\n                      sp. LPS resulted in the exacerbation of Th2\u2010dependent airway inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our results indicate that\n                      <jats:italic>Brasilonema<\/jats:italic>\n                      sp. LPS stimulates the production of cytokines both in vitro and in vivo in a TLR4\u2010dependent manner, since the addition of the SPA\u20104 peptide blocks\n                      <jats:italic>Brasilonema<\/jats:italic>\n                      sp. LPS\u2010dependent increases in IL\u20106 and IL\u20108 in vitro and TLR4\u2010deficient mice were refractory to\n                      <jats:italic>Brasilonema<\/jats:italic>\n                      sp. LPS\u2010mediated induction of lung inflammation in vivo. Additionally, both\n                      <jats:italic>E. coli<\/jats:italic>\n                      and\n                      <jats:italic>Brasilonema<\/jats:italic>\n                      sp. LPS exacerbated airway inflammation in a Th2\u2010dependent model of lung inflammation. However,\n                      <jats:italic>Brasilonema<\/jats:italic>\n                      sp. LPS exacerbated Th2\u2010dependent lung inflammation without significant neutrophil infiltration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Despite the altered signaling through TLR4 by cyanobacterium LPS, these data demonstrate that lung inflammation induced by LPS from the cyanobacterium strain,\n                      <jats:italic>Brasilonema<\/jats:italic>\n                      sp., requires TLR4 and exacerbates Th2\u2010dependent lung inflammation. Therefore, novel interventions that target TLR4 may be beneficial in the treatment of LPS\u2010induced lung inflammation from environmental exposure.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70560","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:27:49Z","timestamp":1792672069000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cyanobacterium\n                    <i>Brasilonema<\/i>\n                    sp. LPS Induces Neutrophil Infiltration and Lung Inflammation in a TLR4\u2010Dependent Manner and Exacerbates Th2\u2010Dependent Lung Inflammation"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1598-9267","authenticated-orcid":false,"given":"Julie","family":"Swartzendruber","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology College of Graduate Studies, Midwestern University Downers Grove Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalinda Monroy Del","family":"Toro","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology College of Graduate Studies, Midwestern University Downers Grove Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Alfano","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology College of Graduate Studies, Midwestern University Downers Grove Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Incrocci","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology College of Graduate Studies, Midwestern University Downers Grove Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael V.","family":"Volin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology College of Graduate Studies, Midwestern University Downers Grove Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kallie","family":"Jiang","sequence":"additional","affiliation":[{"name":"Chicago College of Osteopathic Medicine Midwestern University Downers Grove Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8358-4528","authenticated-orcid":false,"given":"Alejandro M. 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