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.
