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Cellular mechanism of intraabdominal abscess formation by Bacteroides fragilis
F C Gibson1, A B Onderdonk, D L Kasper
1Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. fgibson@bics.bwh.harvard.edu
Abstract:
We investigated the cellular mechanism by which Bacteroides fragilis promotes the development of intraabdominal abscesses in experimental models of sepsis. B. fragilis, as well as purified capsular polysaccharide complex (CPC) from this organism, adhered to primary murine mesothelial cells (MMCs) in vitro. The binding of CPC to murine peritoneal macrophage stimulated TNF-alpha production, which when transferred to monolayers of MMCs elicited significant ICAM-1 expression by these cells. This response resulted in enhanced polymorphonuclear leukocyte attachment to MMCs that could be inhibited by Abs specific for TNF-alpha or ICAM-1. Mice treated with TNF-alpha- or ICAM-1-specific Abs failed to develop intraabdominal abscesses following challenge with purified CPC. These results illustrated the role of the CPC in promoting adhesion of B. fragilis to the peritoneal wall and coordinating the cellular events leading to the development of abscesses associated with experimental intraabdominal sepsis.
Insights
Bacteroides fragilis capsular polysaccharide complex (CPC) promotes intraabdominal abscesses by enhancing immune cell adhesion. Inhibiting TNF-alpha or ICAM-1 prevents abscess formation in sepsis models.
Area of Science:
- Microbiology
- Immunology
- Pathogenesis
Background:
- Intraabdominal abscesses are a severe complication of sepsis.
- The role of Bacteroides fragilis in sepsis pathogenesis is not fully understood.
Purpose of the Study:
- To elucidate the cellular mechanisms by which Bacteroides fragilis promotes intraabdominal abscess development.
- To investigate the role of capsular polysaccharide complex (CPC) in this process.
Main Methods:
- In vitro adhesion assays using primary murine mesothelial cells (MMCs) and B. fragilis/CPC.
- Stimulation of murine peritoneal macrophages with CPC to assess TNF-alpha production.
- Evaluation of ICAM-1 expression on MMCs and polymorphonuclear leukocyte (PMN) attachment.
- In vivo studies using mouse models of intraabdominal sepsis treated with specific antibodies.
Main Results:
- B. fragilis and its CPC adhered to MMCs in vitro.
- CPC binding to macrophages stimulated TNF-alpha production.
- TNF-alpha induced ICAM-1 expression on MMCs, enhancing PMN attachment.
- Inhibition of TNF-alpha or ICAM-1 blocked PMN attachment.
- Antibody treatment against TNF-alpha or ICAM-1 prevented abscess formation in vivo.
Conclusions:
- B. fragilis CPC plays a critical role in initiating intraabdominal abscesses.
- The CPC facilitates bacterial adhesion and orchestrates a cellular cascade involving TNF-alpha and ICAM-1.
- Targeting TNF-alpha or ICAM-1 presents a potential therapeutic strategy for sepsis-associated intraabdominal abscesses.