tetano
Editor, Senior Moderator
Sci Rep
. 2025 Nov 18;15(1):40541.
doi: 10.1038/s41598-025-24349-1. Exposure to bacterial lipopolysaccharide aggravates H1N1-mediated lung immunopathology via neutrophil extracellular trap formation
Guiling Yan[SUP] #[/SUP][SUP] 1 [/SUP], Zhongwen Hu[SUP] #[/SUP][SUP] 2 [/SUP], Yuanyuan Peng[SUP] #[/SUP][SUP] 1 [/SUP], Yuqin Tu[SUP] 1 [/SUP], Jingling Xie[SUP] 1 [/SUP], Yuchao Zhong[SUP] 1 [/SUP], Changchun Niu[SUP] 3 4 [/SUP], Yang Luo[SUP] 5 6 7 [/SUP]
Affiliations
Influenza A virus (IAV) is a prevalent pathogen that causes severe respiratory infections worldwide. Currently, the incidence of coinfections between IAV and Gram-negative bacteria has been steadily increasing, and the synergistic interaction between IAV infection and bacterial exposure represents a pivotal risk factor for disease exacerbation. Lipopolysaccharide (LPS), a major Gram-negative bacterial virulence factor, is hypothesized to regulate IAV-induced immune response intensity and disease severity by reshaping the pulmonary immune microenvironment. Here, we established an in vivo coadministration model via intratracheal instillation of low-dose LPS and H1N1 to dissect their synergistic pathogenesis. LPS exposure potentiated H1N1-induced severe lung injury, manifested as persistent neutrophil and monocyte infiltration, elevated levels of cytokines (e.g., CXCL1, CCL2, and IL-6), and alveolar damage without affecting viral replication. Mechanistically, LPS triggered immune hyperactivation through early neutrophil recruitment, neutrophil extracellular trap (NET) formation, and a self-sustaining positive feedback loop. Intervention experiments revealed that the degradation of NETs by DNase I or neutrophil inhibition significantly alleviated lung damage and systemic inflammatory responses. This study establishes NET-driven innate immune amplification as a key mechanism underlying LPS-enhanced H1N1 pathogenicity, offers an immunomodulatory approach for severe bacterial-viral coinfections, and underscores the parity of immunomodulatory therapy with anti-infective treatment.
Keywords: Bacteria; Inflammatory cytokines; Influenza; Neutrophil extracellular traps; Synergistic effects.
. 2025 Nov 18;15(1):40541.
doi: 10.1038/s41598-025-24349-1. Exposure to bacterial lipopolysaccharide aggravates H1N1-mediated lung immunopathology via neutrophil extracellular trap formation
Guiling Yan[SUP] #[/SUP][SUP] 1 [/SUP], Zhongwen Hu[SUP] #[/SUP][SUP] 2 [/SUP], Yuanyuan Peng[SUP] #[/SUP][SUP] 1 [/SUP], Yuqin Tu[SUP] 1 [/SUP], Jingling Xie[SUP] 1 [/SUP], Yuchao Zhong[SUP] 1 [/SUP], Changchun Niu[SUP] 3 4 [/SUP], Yang Luo[SUP] 5 6 7 [/SUP]
Affiliations
- PMID: 41254009
- DOI: 10.1038/s41598-025-24349-1
Influenza A virus (IAV) is a prevalent pathogen that causes severe respiratory infections worldwide. Currently, the incidence of coinfections between IAV and Gram-negative bacteria has been steadily increasing, and the synergistic interaction between IAV infection and bacterial exposure represents a pivotal risk factor for disease exacerbation. Lipopolysaccharide (LPS), a major Gram-negative bacterial virulence factor, is hypothesized to regulate IAV-induced immune response intensity and disease severity by reshaping the pulmonary immune microenvironment. Here, we established an in vivo coadministration model via intratracheal instillation of low-dose LPS and H1N1 to dissect their synergistic pathogenesis. LPS exposure potentiated H1N1-induced severe lung injury, manifested as persistent neutrophil and monocyte infiltration, elevated levels of cytokines (e.g., CXCL1, CCL2, and IL-6), and alveolar damage without affecting viral replication. Mechanistically, LPS triggered immune hyperactivation through early neutrophil recruitment, neutrophil extracellular trap (NET) formation, and a self-sustaining positive feedback loop. Intervention experiments revealed that the degradation of NETs by DNase I or neutrophil inhibition significantly alleviated lung damage and systemic inflammatory responses. This study establishes NET-driven innate immune amplification as a key mechanism underlying LPS-enhanced H1N1 pathogenicity, offers an immunomodulatory approach for severe bacterial-viral coinfections, and underscores the parity of immunomodulatory therapy with anti-infective treatment.
Keywords: Bacteria; Inflammatory cytokines; Influenza; Neutrophil extracellular traps; Synergistic effects.