Can mycotoxins and persistent infection signals prime autoimmunity?

Environmental and infectious stressors frequently co-occur, synergistically driving chronic inflammatory and autoimmune pathologies. Accumulating research highlights how mycotoxins and persistent pathogens systematically disable host defenses and physiological barriers.

Mechanisms of immune priming and barrier disruption

• Innate activation: Mycotoxins (such as aflatoxins, ochratoxin A, and trichothecenes) upregulate transcripts for MyD88, TLR2, TLR4, and CD14, activating the NLRP3 inflammasome, NF-κB, and MAPK pathways. Concurrently, persistent pathogens like Borrelia burgdorferi maintain chronic pattern recognition receptor (PRR) signaling.
• Barrier degradation: Mycotoxins degrade tight junction proteins (claudins, occludin, ZO-1) through oxidative stress and MLCK/RhoA activation, while infectious inflammatory cytokines (TNF and IL-17) downregulate and mislocalize these same structural proteins.
• Pathogenic feedback loops: Disrupted barriers permit systemic translocation of luminal antigens and endotoxins, exacerbating innate activation. Simultaneously, mycotoxins impair pathogen clearance by dampening TLR signaling and reducing macrophage activity, allowing persistent infections to sustain ongoing immune signals.

Pathways to autoreactivity

• Erosion of tolerance: Chronic PRR activation and barrier leakage shift the immune profile toward a Th1/Th17-skewed response and cause a relative Treg insufficiency, which erodes immunological tolerance and drives epitope spreading.
• Antigenic triggers: While persistent infections trigger autoreactivity via molecular mimicry (where pathogen antigens resemble host proteins), small-molecule mycotoxins promote autoimmunity by forming neoantigen tissue adducts and permitting a systemic flood of external antigens across compromised mucosal barriers.

Bottom line

• Bottom line: Mycotoxins and persistent infections function as convergent environmental stressors that disrupt physiological barriers and prime innate immunity, establishing a feed-forward inflammatory state that promotes epitope spreading and autoreactive responses.