ACR2013: More familiar as a suspect in Alzheimer disease, amyloid proteins may trigger autoantibodies in lupus when introduced via infection, a mouse study suggests.
A bacterial amyloid with the endearing name of curli that forms part of microbial biofilms is implicated a possible cause of lupus in studies using a mouse model of the disease at Temple University. The link to human lupus is less than purely theoretical, say researchers in the abstract of their scheduled presentation at the American College of Rheumatology annual meeting, because humans are exposed to curli during urinary tract and gastrointestinal infections.
The controlled experiment exposed wild-type and lupus-prone NZBW F1 mice to either curli derived from Salmonella cultures or to phosphate-buffered saline, injected intraperitoneally three times a week for five weeks, and then watched for the development of autoantibodies. The team found that immune cells (bone marrow-derived dendritic cells, to be specific) responded strongly to the presence of curli, producing "large quantities" of the interleukins IL-6, IL-10, and IL-12. Dendritic cells from the lupus-prone mice overexpressed interferon-producing genes compared to wild type.
Curli synergizes with DNA in the creation of biofilms, and the lupus-prone mice produced high quantities of autoantibodies to chromatin and nucleic acid after the injections of curli.
The upshot: In lupus-susceptible humans, nucleic acid-containing bacterial amyloids ininfectious biofilms may be an important environmental trigger for autoantibody reactions.