Unraveling the Gut-Lung Axis: Intestinal Flagellin as a Driver of Multisystem Inflammation via the TLR5-IL-15-ARA Pathway

Expansion of intestinal flagellated bacteria represents a shared microbial signature across long COVID, rheumatoid arthritis (RA), ankylosing spondylitis (AS), and inflammatory bowel disease (IBD).
Flagellin activates toll-like receptor 5 (TLR5) on neutrophils, triggering neutrophil extracellular trap (NET) formation and IL-15 release, key drivers of systemic inflammation.
IL-15 stimulates macrophages to produce arachidonic acid (ARA), linking innate immune activation to lipid-mediated inflammatory responses.
Interventions targeting the TLR5-IL-15-ARA axis, including genetic ablation and microbiome modulation, effectively attenuate multisystem pathology in a SARS-CoV-2 and Pseudomonas murine co-infection model.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Expansion of intestinal flagellated bacteria represents a shared microbial signature across long COVID, rheumatoid arthritis (RA), ankylosing spondylitis (AS), and inflammatory bowel disease (IBD).
Flagellin activates toll-like receptor 5 (TLR5) on neutrophils, triggering neutrophil extracellular trap (NET) formation and IL-15 release, key drivers of systemic inflammation.
IL-15 stimulates macrophages to produce arachidonic acid (ARA), linking innate immune activation to lipid-mediated inflammatory responses.
Interventions targeting the TLR5-IL-15-ARA axis, including genetic ablation and microbiome modulation, effectively attenuate multisystem pathology in a SARS-CoV-2 and Pseudomonas murine co-infection model.

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