1002 Bacterial amyloid curli/eDNA complexes induce NETosis in lupus patients positive for anti-dsDNA

Infections are a major contributor to lupus disease. Uropathogenic E. coli (UPEC) is responsible for the majority of urinary tract infections in both healthy individuals and patients. We have previously demonstrated that bacterial amyloid curli complexes curli/DNA, produced by E.coli, can accelerate disease mouse models lupus. Moreover we extended these findings human demonstrate curli/DNA mimic autoantigens patients with chronic bacteriuria high levels anti-curli/DNA higher anti-dsDNA, more flares proinflammatory profile. These suggest subclinical might be trigger propagator autoimmunity via activation innate adaptive immune system. Based on our previous results, hypothesize exposure UPEC containing curli/eDNA could also activate neutrophils, first responders infections, specifically generation neutrophil extracellular traps (NETs), fundamental mechanism clear bacteria recently appreciated pathogenic Neutrophil (NETs) part system SLE. therefore investigated 56 who met at least 4 SLICC criteria. Results were compared 20 age, sex, race matched controls. found induced NETs SLE PMNs In SLE, inducers triggered inducer LPS PMA. Interestingly, anti- dsDNA positive made response complexes. Moreover, anti-dsDNA responded highly LPS. did not observe this negative. Mechanistically, induce NADPH oxidase. Finally, had amount NET production PMA no bacteriuria. conclude 1) inflammatory state. And 2) neutrophils UPECs sustain form traps.