Responses to Amyloids of Microbial and Host Origin Are Mediated through Toll-like Receptor 2

Çagla Tükel, R. Paul Wilson, Jessalyn H. Nishimori, Milad Pezeshki, Brett A. Chromy, Andreas J Baumler

Research output: Contribution to journalArticlepeer-review

112 Scopus citations


Curli fibrils are proteinaceous bacterial structures formed by amyloid fibrils composed of the major curli subunit CsgA. Like β-amyloid 1-42, which is associated with brain inflammation and Alzheimer's disease, curli fibrils have been implicated in the induction of host inflammatory responses. However, the underlying mechanisms of amyloid-induced inflammation are not fully understood. In a mouse sepsis model, we show that curli fibrils contributed to Nos2 expression, a hallmark of inflammation, by stimulating Toll-like receptor (TLR) 2. The TLR2 agonist activity was reduced by an amyloidogenicity-lowering amino acid substitution (N122A) in CsgA. Amyloid-forming synthetic peptides corresponding to β-amyloid 1-42 or CsgA 111-151 stimulated Nos2 production in macrophages and microglia cells through a TLR2-dependent mechanism. This activity was abrogated when an N122A substitution was introduced into the synthetic CsgA peptide. The induction of TLR2-mediated responses by bacterial and eukaryotic amyloids may explain the inflammation associated with amyloids and the resulting pathologies.

Original languageEnglish (US)
Pages (from-to)45-53
Number of pages9
JournalCell Host and Microbe
Issue number1
StatePublished - Jul 23 2009



ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology


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