In vivo synthesis of bacterial amyloid curli contributes to joint inflammation during S. Typhimurium infection

Autor: Çagla Tükel, Melissa B. Palmer, Ryan Krochak, Nicole J. Medeiros, Lauren K. Nicastro, Nikole L. Watson, Elizabeth G. Hansen, Keith D. MacKenzie, Yi Zhang, Sarah A. Tursi, Aaron White, Heather L. Wilson, Amanda L. Miller, Dakoda J. Herman, Akosiererem S. Sokaribo, R. Paul Wilson, J. Alex Pasternak
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Bacterial Diseases
Salmonellosis
Physiology
Arthritis
Pathology and Laboratory Medicine
Biochemistry
Mice
Salmonella
Immune Physiology
Medicine and Health Sciences
Gastrointestinal Infections
Enzyme-Linked Immunoassays
Biology (General)
0303 health sciences
Immune System Proteins
030302 biochemistry & molecular biology
Pattern recognition receptor
Animal Models
Bacterial Pathogens
3. Good health
Infectious Diseases
Experimental Organism Systems
Medical Microbiology
Salmonella enterica
Antibodies
Antinuclear
Salmonella Typhimurium
Pathogens
Anatomy
medicine.symptom
Research Article
Amyloid
QH301-705.5
Immunology
Mouse Models
Inflammation
Gastroenterology and Hepatology
Biology
Research and Analysis Methods
Microbiology
Antibodies
03 medical and health sciences
Model Organisms
Immune system
Enterobacteriaceae
Bacterial Proteins
Virology
Genetics
medicine
Animals
Intestine
Large
Typhoid Fever
Immunoassays
Microbial Pathogens
Molecular Biology
Autoantibodies
030304 developmental biology
Arthritis
Infectious
Bacteria
Organisms
Autoantibody
Biology and Life Sciences
Proteins
RC581-607
biology.organism_classification
medicine.disease
Arthritis
Experimental
Gastrointestinal Tract
Chronic infection
Animal Studies
Immunologic Techniques
Parasitology
Immunologic diseases. Allergy
Digestive System
Zdroj: PLoS Pathogens, Vol 16, Iss 7, p e1008591 (2020)
PLoS Pathogens
ISSN: 1553-7374
1553-7366
Popis: Reactive arthritis, an autoimmune disorder, occurs following gastrointestinal infection with invasive enteric pathogens, such as Salmonella enterica. Curli, an extracellular, bacterial amyloid with cross beta-sheet structure can trigger inflammatory responses by stimulating pattern recognition receptors. Here we show that S. Typhimurium produces curli amyloids in the cecum and colon of mice after natural oral infection, in both acute and chronic infection models. Production of curli was associated with an increase in anti-dsDNA autoantibodies and joint inflammation in infected mice. The negative impacts on the host appeared to be dependent on invasive systemic exposure of curli to immune cells. We hypothesize that in vivo synthesis of curli contributes to known complications of enteric infections and suggest that cross-seeding interactions can occur between pathogen-produced amyloids and amyloidogenic proteins of the host.
Author summary Our manuscript focuses on curli, a ‘functional amyloid’ produced by Salmonella as well as other enteric bacteria. We present the first biochemical evidence that these fibers are produced in the gastrointestinal tract of mice after oral infection, the natural route for Salmonella infections. This finding is significant because of the immune impacts on the host; we show that curli cause an increase in autoimmunity and inflammation in the knee joints of infected mice. Reactive arthritis is a known autoimmune complication after enteric infections and our results indicate that presence of curli in the gut provides a novel linchpin of pathogenesis. As curli or curli-like amyloids are also produced by the commensal bacteria, it is possible that the unintended release of amyloids produced by the microbiota could trigger similar autoimmune reactions. Finally, our work provides conceptual evidence for the possibility of cross-seeding between bacterial amyloids like curli and human amyloids involved in amyloid-associated diseases such as Alzheimer’s Disease via the gut microbiome or infections.
Databáze: OpenAIRE
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