Salmonella infection and biofilms drive anti-C1q and anti-dsDNA autoantibodies in systemic autoimmunity
4 affiliations
- 1Center for Microbiology and Immunology, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania, United States of America
- 2Division of Rheumatology, Department of Medicine, UMass Chan Medical School, Worcester, Massachusetts, United States of America
- 3Durham VA Medical Center and Duke University Medical Center, Durham, North Carolina, United States of America
- 4Department of Medicine, NYU Grossman School of Medicine, New York, New York, United States of America
Abstract
Systemic lupus erythematosus (SLE) is characterized by autoantibody production alongside inflammatory manifestations, including nephritis. In SLE, infections are frequent and associated with disease flares, increasing morbidity and mortality. Additionally, dysbiosis, often marked by overgrowth of Pseudomonadota, is a prominent feature of SLE and lupus nephritis. We previously demonstrated that complexes of DNA and curli, an amyloidogenic protein from biofilms of Pseudomonadota, including Salmonella Typhimurium and E. coli, can induce anti-dsDNA and anti-chromatin autoantibody responses. Here, we assessed the effects of curli administration or Salmonella infection on autoimmune manifestations in wild-type and lupus-prone mice. A multiplex autoantibody assay showed increased levels of anti-C1q antibodies in curli-treated C57BL/6 and lupus-prone NZBxW/F1 mice compared to PBS-treated controls. An anti-C1q-specific ELISA confirmed the presence of anti-C1q antibodies in C57BL/6 mice after treatment with curli/DNA, extracted from E. coli or Salmonella biofilms, or infection with Salmonella. Prior to the onset of spontaneous disease, sera from young NZBxW/F1 mice, injected with curli, demonstrated increased anti-dsDNA and anti-C1q antibody responses compared to PBS-treated controls; however, no differences were found in older mice, post-onset, when autoantibody levels were already high. In MRL/lpr mice, curli treatment significantly exacerbated anti-C1q antibody production regardless of age and disease stage, compared to PBS-treated controls. While curli treatment did not significantly affect proteinuria in either model, curli-treatment of MRL/lpr mice significantly increased C1q deposition in glomeruli. This study uncovers a novel mechanism for the induction of anti-C1q autoantibodies and how infection or dysbiosis may exacerbate renal disease in SLE. Author summary: Up to half of patients with systemic lupus erythematosus (SLE) develop lupus nephritis, a major cause of morbidity characterized by immune complex deposition and complement activation within the glomeruli. The deposition of immune complexes is thought to contribute to the development of kidney inflammation and injury. Our previous work found a link between anti-DNA antibody production and exposure to the biofilm matrices of bacteria like Salmonella and E. coli. Such bacterial infections or microbiota species overgrowths are associated with autoimmunity. Here, we found, for the first time, that purified biofilm matrix or Salmonella infection triggers the production of antibodies targeting C1q in both healthy and lupus-prone mouse models. Additionally, we showed that biofilm matrix administration increased C1q deposition in the glomeruli of lupus-prone mice, implicating bacterial biofilms in the exacerbation of lupus nephritis. This work highlights the interplay between environmental insults like bacterial infections, age, and the development or exacerbation of autoimmunity, in genetically predisposed individuals.
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BibTeX
@article{grando2026salmonella,
title = {{Salmonella infection and biofilms drive anti-C1q and anti-dsDNA autoantibodies in systemic autoimmunity}},
author = {Kaitlyn Grando and Molly Elkins and Lauren Nicastro and Shingo Bessho and Sophia Olubajo and Anita Kowal and Vincent Tam and Roberto Caricchio and David Pisetsky and Gregg J. Silverman and Çagla Tükel},
journal = {PLOS Pathogens},
year = {2026},
month = oct,
doi = {10.1371/journal.ppat.1014666},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014666},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Salmonella infection and biofilms drive anti-C1q and anti-dsDNA autoantibodies in systemic autoimmunity
AU - Kaitlyn Grando
AU - Molly Elkins
AU - Lauren Nicastro
AU - Shingo Bessho
AU - Sophia Olubajo
AU - Anita Kowal
AU - Vincent Tam
AU - Roberto Caricchio
AU - David Pisetsky
AU - Gregg J. Silverman
AU - Çagla Tükel
PY - 2026
DA - 2026/10/01
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014666
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014666
AB - Systemic lupus erythematosus (SLE) is characterized by autoantibody production alongside inflammatory manifestations, including nephritis. In SLE, infections are frequent and associated with disease flares, increasing morbidity and mortality. Additionally, dysbiosis, often marked by overgrowth of Pseudomonadota, is a prominent feature of SLE and lupus nephritis. We previously demonstrated that complexes of DNA and curli, an amyloidogenic protein from biofilms of Pseudomonadota, including Salmonella Typhimurium and E. coli, can induce anti-dsDNA and anti-chromatin autoantibody responses. Here, we assessed the effects of curli administration or Salmonella infection on autoimmune manifestations in wild-type and lupus-prone mice. A multiplex autoantibody assay showed increased levels of anti-C1q antibodies in curli-treated C57BL/6 and lupus-prone NZBxW/F1 mice compared to PBS-treated controls. An anti-C1q-specific ELISA confirmed the presence of anti-C1q antibodies in C57BL/6 mice after treatment with curli/DNA, extracted from E. coli or Salmonella biofilms, or infection with Salmonella. Prior to the onset of spontaneous disease, sera from young NZBxW/F1 mice, injected with curli, demonstrated increased anti-dsDNA and anti-C1q antibody responses compared to PBS-treated controls; however, no differences were found in older mice, post-onset, when autoantibody levels were already high. In MRL/lpr mice, curli treatment significantly exacerbated anti-C1q antibody production regardless of age and disease stage, compared to PBS-treated controls. While curli treatment did not significantly affect proteinuria in either model, curli-treatment of MRL/lpr mice significantly increased C1q deposition in glomeruli. This study uncovers a novel mechanism for the induction of anti-C1q autoantibodies and how infection or dysbiosis may exacerbate renal disease in SLE. Author summary: Up to half of patients with systemic lupus erythematosus (SLE) develop lupus nephritis, a major cause of morbidity characterized by immune complex deposition and complement activation within the glomeruli. The deposition of immune complexes is thought to contribute to the development of kidney inflammation and injury. Our previous work found a link between anti-DNA antibody production and exposure to the biofilm matrices of bacteria like Salmonella and E. coli. Such bacterial infections or microbiota species overgrowths are associated with autoimmunity. Here, we found, for the first time, that purified biofilm matrix or Salmonella infection triggers the production of antibodies targeting C1q in both healthy and lupus-prone mouse models. Additionally, we showed that biofilm matrix administration increased C1q deposition in the glomeruli of lupus-prone mice, implicating bacterial biofilms in the exacerbation of lupus nephritis. This work highlights the interplay between environmental insults like bacterial infections, age, and the development or exacerbation of autoimmunity, in genetically predisposed individuals.
SN - 1553-7374
ER -