Cellular immunity to Bacteroides fragilis capsular polysaccharide.

Abstract

Bacteroidesfragilis, an anaerobic bacterium that accounts for only a small fraction of the colonic microflora, is the most frequently isolated anaerobic species in many infectious processes (1), including intraabdominal sepsis (2). Strains of B. fragilis have a polysaccharide antigen on their surface that is not present on other Bacteroides species (3, 4). B. fragilis is unique among anaerobes in its ability to induce abscesses by itself, and in a rat model of intraabdominal sepsis, this ability has been shown to be dependent upon the presence of the polysaccharide capsule (5, 6). It has been shown that rats immunized with this capsular polysaccharide (CP) 1 are protected from intraabdominal abscess formation and bacteremia caused by this organism (7). In the rat, this protection can be passively transferred by nylon wool nonadherent spleen cells (8).To better define the immune response to B. fragilis, we have developed a new experimental model for intraabdominal sepsis using the mouse. This model has several features that make it preferable to other previously described model systems (5, 9). The rat model of intraabdominal sepsis (5) has the disadvantage of requiring surgical implantation of the inoculum, and both a gelatin capsule and BaSO4 are required in order to obtain uniform abscess development. The murine model described by Joiner et al. (9) involved subcutaneous implantation of the inoculum, resulting in subcutaneous abscesses at the site of inoculation. The model described below more closely parallels disease in humans because no vehicle is required, and the result is intraperitoneal abscess formation. The use of sterile cecal contents provides a medium similar to that encountered in naturally occurring intraabdominal sepsis.In the studies detailed below, we have shown that mice immunized with CP are immune to the development of abscesses, and that this immunity is a function of T cells. The immune response is mediated by an antigen-specific, but non-H-2-restricted Ly-l-2 + cell. The application of this model to the study of immune responses to Tindependent polysaccharides is discussed.

T lymphocyte-mediated protection against Pseudomonas aeruginosa infection in granulocytopenic mice.

“…(17,18). Our studies and those of others (19,20) clearly indicate that PSactivated T cells may function not merely as regulatory cells but also as effector cells in resistance to bacterial infection.…”

Orientations of theBacteroides fragilisCapsular Polysaccharide Biosynthesis Locus Promoters during Symbiosis and Infection

“…The abscess model was performed similarly to a model previously described (19). Briefly, 6-to 8-week-old male C57BL/6J mice from Jackson Laboratory (Bar Harbor, ME) were injected intraperitoneally with B. fragilis (1 ϫ 10 8 CFU/mouse) mixed with sterile rat cecal contents (1:1, vol/vol, 0.2 ml total volume), which mimics the spillage of colonic contents into the peritoneal cavity (14,17). Seven days later, intra-abdominal abscesses were excised and processed for bacterial DNA isolation.…”

Bacteroides: the Good, the Bad, and the Nitty-Gritty

“…Injection of capsules alone was sufficient to induce abscess formation (67), while systemic injection prevented abscess formation in rats, presumably due to antibody development and subsequent protection (281). Responses to most other polysaccharide antigens are T-cell independent, but abscess formation induced by B. fragilis is dependent on T cells (243)(244)(245)310).…”