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Immune mechanisms in the prevention of intra-abdominal abscess formation
D L Kasper1, R F Finberg, J Crabb
1Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts.
Abstract:
Bacteroides fragilis is the most commonly isolated anaerobe from intraabdominal infections. In experimental models of intraabdominal sepsis, B. fragilis has been shown to be uniquely virulent. Some of these virulence traits are due to the capsular polysaccharide of this organism. Immunity to infection secondary to B. fragilis seems to involve both arms of the immune system. Humoral immunity (complement, antibody and PMNs) is critical to clearance of these bacteria from the blood stream. Cellular immune mechanisms predominate against intraabdominal abscess formation. Adoptive transfer experiments have shown that a CD8+, IJ+, non H2 restricted immune T cell or lysate from this T cell confers protection to immunocompetent, naive mice. An in vivo system has been developed to begin defining the mechanism of protection. B. fragilis placed inside a filter containment chamber within the peritoneum of immune mice are specifically killed over an 8-day period in the absence of white blood cells. This killing phenomenon was also observed inside filter chambers within mice receiving adoptively transferred immune T cells or lysates of these T cells. Furthermore, killing is specific to B. fragilis. These results support a T cell dependent mechanism for killing this bacteria and provide an interesting model for further exploration.
Insights
Immune T cells, not white blood cells, specifically kill the virulent bacterium Bacteroides fragilis in a novel mouse model. This discovery highlights a T cell-dependent mechanism crucial for combating intra-abdominal infections.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Bacteroides fragilis is a common cause of intra-abdominal infections.
- This bacterium exhibits unique virulence, partly due to its capsular polysaccharide.
- Immunity against B. fragilis involves both humoral and cellular immune responses.
Purpose of the Study:
- To investigate the cellular immune mechanisms involved in protection against Bacteroides fragilis infections.
- To define the specific T cell-dependent mechanisms responsible for bacterial clearance.
Main Methods:
- Development of an in vivo model using filter containment chambers in the peritoneum of immune mice.
- Adoptive transfer of immune T cells or their lysates into naive mice.
- Observation of bacterial killing in the absence of white blood cells.
Main Results:
- Bacteroides fragilis was specifically killed within filter chambers in immune mice over 8 days, independent of white blood cells.
- This killing phenomenon was replicated in mice receiving adoptive T cell transfers or T cell lysates.
- The killing mechanism was specific to B. fragilis.
Conclusions:
- A T cell-dependent mechanism is responsible for the specific killing of Bacteroides fragilis.
- This study provides a novel model for further exploring T cell-mediated immunity against this bacterium.