The menace within: bacterial amyloids as a trigger for autoimmune and neurodegenerative diseases

Bacteria are known to produce amyloids, proteins characterized by a conserved cross-beta sheet structure, which exhibit structural and functional similarities to human amyloids. The deposition of human amyloids into fibrillar plaques within organs is closely linked to several debilitating human diseases, including Alzheimer’s and Parkinson’s disease. Recently, bacterial amyloids have garnered significant attention as potential initiators of human amyloid-associated diseases as well as autoimmune diseases.

This review aims to explore how bacterial amyloid, particularly curli found in gut biofilms, can act as a trigger for neurodegenerative and autoimmune diseases. We will elucidate three primary mechanisms through which bacterial amyloids exert their influence:

• 1.

  Direct interaction with human amyloids: Bacterial amyloids can directly interact with human amyloids, potentially accelerating the aggregation and deposition of amyloid fibrils associated with diseases such as Alzheimer’s and Parkinson’s disease. This direct interaction may contribute to the pathological progression of these conditions.

• 2.

  Induction of inflammation: Bacterial amyloids have the capacity to induce inflammatory responses within the host organism. Chronic inflammation is increasingly recognized as a contributor to neurodegenerative and autoimmune diseases. We will explore how the activation of inflammatory pathways and neuroinflammation by bacterial amyloids can exacerbate disease pathogenesis.

• 3.

  Acting as a DNA carrier: Bacterial amyloids may also serve as carriers of DNA, facilitating the activation of host DNA sensors. This mechanism can potentially lead to alterations in the host’s immune response and also contribute to the development of autoantibodies.

By delving into these three distinct modes of action, this review will provide valuable insights into the intricate relationship between bacterial amyloids and the onset or progression of neurodegenerative and autoimmune diseases. A comprehensive understanding of these mechanisms may open new avenues for therapeutic interventions and preventive strategies targeting amyloid-associated diseases.