Bacterial flagellin is a dominant antigen in Crohn disease
Open accessAbstract
Chronic intestinal inflammation, as seen in inflammatory bowel disease (IBD), results from an aberrant and poorly understood mucosal immune response to the microbiota of the gastrointestinal tract in genetically susceptible individuals. Here we used serological expression cloning to identify commensal bacterial proteins that could contribute to the pathogenesis of IBD. The dominant antigens identified were flagellins, molecules known to activate innate immunity via Toll-like receptor 5 (TLR5), and critical targets of the acquired immune system in host defense. Multiple strains of colitic mice had elevated serum anti-flagellin IgG2a responses and Th1 T cell responses to flagellin. In addition, flagellin-specific CD4(+) T cells induced severe colitis when adoptively transferred into naive SCID mice. Serum IgG to these flagellins, but not to the dissimilar Salmonella muenchen flagellin, was elevated in patients with Crohn disease, but not in patients with ulcerative colitis or in controls. These results identify flagellins as a class of immunodominant antigens that stimulate pathogenic intestinal immune reactions in genetically diverse hosts and suggest new avenues for the diagnosis and antigen-directed therapy of patients with IBD.
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The enrichment of Lachnospiraceae, Enterocloster species and R. gnavus after IgG coating may be explained by their flagella or flagellins, which are highly immunogenic and dominant antigens in IBD.
“The observed enrichment of several types of Lachnospiraceae and species from the Enterocloster genus (such as E. bolteae and E. clostridioformis) or R. gnavus after IgG coating could be explained by the fact that these bacteria have flagella or flagellins, which have been reported to be highly immunogenic proteins and dominant antigens in the context of IBD114,115.”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [114]
The humoral immune response to gut microorganisms includes T cell-dependent and T cell-independent memory B cell responses and can be tracked by serological reactivity to common intestinal bacteria.
“The humoral immune response against gut microorganisms encompasses T cell-dependent and T cell-independent memory B cell responses and can be monitored by serological reactivities against prevalent intestinal bacteria113–115.”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [114]
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- Authors
- Lodes, M. J., Cong, Y., Elson, C. O., Mohamath, R., Landers, C. J., Targan, S. R., Fort, M., & Hershberg, R. M.
- Affiliations
- Corixa Corporation (US)
- University of Alabama at Birmingham (US)
- GlaxoSmithKline (United Kingdom) (GB)
- Cedars-Sinai Medical Center (US)
- Infectious Disease Research Institute (US)
- Corresponding author
- Hershberg, Robert M.
- Venue
- Journal of Clinical Investigation
- Published
- 2004-05-01
- Volume
- 113
- Issue
- 9
- Pages
- 1296-1306
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC398429
- OpenAlex
- W2057759034
- Cited by
- 802
- References
- 37
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 19 · 2023: 26 · 2022: 15 · 2021: 21 · 2020: 23 · 2019: 25 · 2018: 27 · 2017: 31 · 2016: 32 · 2015: 30 · 2014: 28 · 2013: 45 · 2012: 49
- FWCI
- 33.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- Locations
- Journal of Clinical Investigation (publishedVersion, public-domain)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (PO1 DK46763, DK46763)
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK046763, P01DK044240)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- bacterial flagellin, Crohn's disease, inflammatory bowel disease, commensal bacteria, immunodominant antigens, TLR5, Th1 cells, colitis, adoptive transfer, mucosal immunity, ulcerative colitis
- MeSH terms
- Animals, Antigen-Presenting Cells, Antigens, Bacterial, Bacterial Proteins, Cecum, Cells, Cultured, Cloning, Molecular, Crohn Disease, Dose-Response Relationship, Immunologic, Escherichia coli, Flagellin, Humans, Immunoglobulin G, Lymphocyte Activation, Mice, Inbred CBA, Mice, Inbred C3H, Molecular Sequence Data, Recombinant Proteins, Time Factors, Inflammatory Bowel Diseases, CD4-Positive T-Lymphocytes, CD4 Antigens, Mice, SCID, Mice
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