Expression of and cytokine activation by Escherichia coli curli fibers in human sepsis

Curli organelles are expressed by commensal Escherichia coli K12 and by Sal monella typhimurium at temperatures <37 degrees C, which bind serum protein s and activate the contact-phase system in vitro. This study demonstrates, by means of an anti-CsgA (curli major subunit) antibody that a significant fraction of E. coli isolates (24 of 46) from human blood cultures produce c urli at 37 degrees C in vitro. Serum samples from 12 convalescent patients with sepsis, but not serum from healthy controls, contained antibodies agai nst CsgA (n = 12). This study further demonstrates that a curli-expressing E: coli strain and a noncurliated mutant secreting soluble CsgA induce sign ificantly (P <.05) higher levels of proinflammatory cytokines (tumor necros is factor-alpha, interleukin [IL]-6, and IL-8) in human macrophages differe ntiated from THP-1 cells. These data, therefore, provide direct evidence th at curli are expressed in vivo in human sepsis and suggest a possible role for curli and CsgA in the induction of proinflammatory cytokines during E. coli sepsis.