Work

Cyanobacterium Brasilonema sp. LPS Induces Neutrophil Infiltration and Lung Inflammation in a TLR4‐Dependent Manner and Exacerbates Th2‐Dependent Lung Inflammation

Year: 2026

Type: article

Abstract: BACKGROUND: Chronic airway inflammation can be induced by both chemical and environmental factors. Airway inflammation can be induced through different immune pathways, including allergic Th2-dependent activation of eosinophils and mast cells, Th1/Th17-dependent 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-mediated lung inflammation is cyanobacterium lipopolysaccharide (LPS). The study has two main objectives: first to determine whether TLR4 is required for cyanobacterium LPS-induced 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-dependent mouse model of airway hypersensitivity. METHODS: LPS from the cyanobacterium strain, Brasilonema sp., was purified and used for both in vivo and in vitro assays. For in vitro assays, the TLR4 inhibitor, SPA-4, was assessed in its ability to block Brasilonema sp.-dependent IL-6 and IL-8 induction in lung epithelial cell lines, and in vivo, the ability of Brasilonema sp. LPS to induce lung inflammation was assessed in TLR4-deficient mice in comparison to controls. Finally, Th2-driven lung inflammation was established using ovalbumin and then these mice were exposed to Brasilonema sp. LPS intranasally to assess if Brasilonema sp. LPS resulted in the exacerbation of Th2-dependent airway inflammation. RESULTS: Our results indicate that Brasilonema sp. LPS stimulates the production of cytokines both in vitro and in vivo in a TLR4-dependent manner, since the addition of the SPA-4 peptide blocks Brasilonema sp. LPS-dependent increases in IL-6 and IL-8 in vitro and TLR4-deficient mice were refractory to Brasilonema sp. LPS-mediated induction of lung inflammation in vivo. Additionally, both E. coli and Brasilonema sp. LPS exacerbated airway inflammation in a Th2-dependent model of lung inflammation. However, Brasilonema sp. LPS exacerbated Th2-dependent lung inflammation without significant neutrophil infiltration. CONCLUSIONS: Despite the altered signaling through TLR4 by cyanobacterium LPS, these data demonstrate that lung inflammation induced by LPS from the cyanobacterium strain, Brasilonema sp., requires TLR4 and exacerbates Th2-dependent lung inflammation. Therefore, novel interventions that target TLR4 may be beneficial in the treatment of LPS-induced lung inflammation from environmental exposure.

Source: Immunity Inflammation and Disease

DOI: 10.1002/iid3.70560