Cyanobacterium Brasilonema sp. LPS Induces Neutrophil Infiltration and Lung Inflammation in a TLR4-Dependent Manner and Exacerbates Th2-Dependent Lung Inflammation.
4 affiliations
- 1Department of Microbiology and Immunology, College of Graduate Studies, Midwestern University, Downers Grove, Illinois, USA.
- 2Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, Illinois, USA.
- 3Department of Pharmacology, College of Graduate Studies, Midwestern University, Downers Grove, Illinois, USA.
- 4Department of Chemistry, University of Hawai'i-Mānoa, Honolulu, Hawaii, USA.
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.
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BibTeX
@article{swartzendruber2026cyanobacterium,
title = {{Cyanobacterium Brasilonema sp. LPS Induces Neutrophil Infiltration and Lung Inflammation in a TLR4-Dependent Manner and Exacerbates Th2-Dependent Lung Inflammation.}},
author = {Julie Swartzendruber and Rosalinda Monroy Del Toro and Peter Alfano and Ryan Incrocci and Michael V Volin and Kallie Jiang and Alejandro M S Mayer and Philip G Williams and Timothy J O'Donnell and Michelle Swanson-Mungerson},
journal = {Immunity, inflammation and disease},
year = {2026},
month = oct,
doi = {10.1002/iid3.70560},
url = {https://europepmc.org/article/MED/42910835},
note = {CC BY},
}
RIS
TY - JOUR
TI - Cyanobacterium Brasilonema sp. LPS Induces Neutrophil Infiltration and Lung Inflammation in a TLR4-Dependent Manner and Exacerbates Th2-Dependent Lung Inflammation.
AU - Julie Swartzendruber
AU - Rosalinda Monroy Del Toro
AU - Peter Alfano
AU - Ryan Incrocci
AU - Michael V Volin
AU - Kallie Jiang
AU - Alejandro M S Mayer
AU - Philip G Williams
AU - Timothy J O'Donnell
AU - Michelle Swanson-Mungerson
PY - 2026
DA - 2026/10/01
JO - Immunity, inflammation and disease
DO - 10.1002/iid3.70560
UR - https://europepmc.org/article/MED/42910835
AB - 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.
SN - 2050-4527
ER -