title: Biofilm-associated bacterial amyloids dampen inflammation in the gut: oral treatment with curli fibres reduces the severity of hapten-induced colitis in mice.
abstract: OBJECTIVE
  A disruption of epithelial barrier function can lead to intestinal inflammation. Toll-like receptor (TLR) 2 activation by microbial products promotes intestinal epithelial integrity and overall gut health. Several bacterial species, including enteric bacteria, actively produce amyloid proteins as a part of their biofilms. Recognition of amyloid fibres found in enteric biofilms, termed curli, by the Toll-like receptor (TLR)2/1 complex reinforces barrier function. Here, we investigated the effect of purified curli fibres on inflammation in a mouse model of acute colitis.
  
  
  METHODS
  Bone marrow-derived macrophages as well as lamina propria cells were treated with curli fibres of both pathogenicSalmonella entericaserovar Typhimurium and commensalEscherichia coliNissle 1917 biofilms. Mice were given 0.1 or 0.4 mg of purified curli orally 1 day post administration of 1% 2,4,6-trinitrobenzene sulphonic acid (TNBS) enema. Histopathological analysis was performed on distal colonic tissue taken 6 days post TNBS enema. RNA extracted from colonic tissue was subjected to RT-PCR.
  
  
  RESULTS
  Here we show that curli fibres of both pathogenic and commensal bacteria are recognised by TLR2 leading to the production of IL-10, immunomodulatory cytokine of intestinal homeostasis. Treatment of mice with a single dose of curli heightens transcript levels ofIl10in the colon and ameliorates the disease pathology in TNBS-induced colitis. Curli treatment is comparable to the treatment with anti-tumour necrosis factor alpha (anti-TNFα) antibodies, a treatment known to reduce the severity of acute colitis in humans and mice.
  
  
  CONCLUSIONS
  These results suggest that the bacterial amyloids had a role in helping to maintain immune homeostasis in the intestinal mucosa via the TLR2/IL-10 axis. Furthermore, bacterial amyloids may be a potential candidate therapeutic to treat intestinal inflammatory disorders owing to their remarkable immunomodulatory activity.
authors: Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, PA, USA.
authors: Gertrude O
authors: GO
authors: Oppong
authors: Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, PA, USA.
authors: Glenn J
authors: GJ
authors: Rapsinski
authors: Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, PA, USA.
authors: Sarah A
authors: SA
authors: Tursi
authors: Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, PA, USA.
authors: Steven G
authors: SG
authors: Biesecker
authors: Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA, USA.
authors: Andres Jp
authors: AJ
authors: Klein-Szanto
authors: Department of Biology, University of Pennsylvania, Philadelphia, PA, USA.
authors: Mark
authors: M
authors: Goulian
authors: Janssen Research & Development, LLC, Spring House, PA, USA.
authors: Christine
authors: C
authors: McCauley
authors: Janssen Research & Development, LLC, Spring House, PA, USA.
authors: Catherine
authors: C
authors: Healy
authors: Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, PA, USA.
authors: R Paul
authors: RP
authors: Wilson
authors: Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, PA, USA.
authors: Cagla
authors: C
authors: Tükel