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Recent microbiome studies have shown that\n                      <jats:italic>Haemophilus influenzae<\/jats:italic>\n                      is frequently co-detected in severe RSV cases and ranks among the bacteria most closely correlated with disease severity; however, its causal role and underlying mechanisms remain unclear. Here, we used a murine model to examine the manner in which\n                      <jats:italic>H. influenzae<\/jats:italic>\n                      influences RSV-associated airway inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We established a murine respiratory infection model by infecting mice with RSV and subsequently intratracheally inoculating them with live, ultraviolet (UV)-killed, or heat-killed nontypeable\n                      <jats:italic>H. influenzae<\/jats:italic>\n                      (NTHi). Body weight, viral and bacterial loads, bronchoalveolar lavage fluid (BALF) cytokine levels, and immune cell populations were analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Live NTHi inoculation following RSV infection induced severe lower airway inflammation, characterized by pronounced body weight loss and lung injury along with increased CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell accumulation and enhanced interleukin (IL)-6 inflammatory mediator production in BALF. Additionally, CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell depletion modestly attenuated body weight loss, altered the recruited innate immune cell composition, and reduced BALF IL-6 levels. However, RSV-infected mice inoculated with UV- or heat-killed NTHi exhibited CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell accumulation without developing body weight loss, which suggested that CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell accumulation alone may be insufficient to drive full disease manifestation. In contrast to that observed for non-viable NTHi, live NTHi induced robust neutrophil recruitment along with strong production of inflammatory mediators. Additionally, BALF IL-6 levels showed a strong negative correlation with body weight; hence, IL-6 was identified as a potential marker associated with disease severity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This mouse model shows that pulmonary inoculation of live NTHi after RSV infection induces severe lower airway inflammation partially involving CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and that IL-6 is a potential biomarker associated with disease severity. Overall, this study suggests a novel pathological role for NTHi in the exacerbation mechanism of secondary bacterial infection in RSV infection.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12931-026-03774-4","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T07:54:59Z","timestamp":1781942099000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Live nontypeable Haemophilus influenzae exacerbates respiratory syncytial virus-associated lower airway inflammation"],"prefix":"10.1186","volume":"27","author":[{"given":"Eigo","family":"Kawahara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Morimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. 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