Reduced bacterial dissemination and liver injury in CD14-deficient mice following a chronic abscess-forming peritonitis induced by Bacteroides fragilis

Abstract

The CD14 myelomonocytic differentiation antigen plays a major role in acute Gram-negative infections with Escherichia coli; however, its role in chronic infections has not yet been analyzed. To address this question, we studied the role of CD14 in a chronic abscess-forming peritonitis, induced by Bacteroides fragilis. B. fragilis (3x10(8) CFU/ml) were resuspended in a liquid nutrient agar and injected into the peritoneal cavity of CD14-deficient (CD 14-/-) and normal C57BL/6J (CD 14+/+) mice, respectively. After 3 days there was a severe phlegmonous intra-abdominal inflammation in both groups. After 7 days an abscess-forming peritonitis developed and by 14 days the infectious foci were compartimentalized. These observations were indistinguishable between CD14-/- and CD14+/+ mice. Although no differences were seen in abscess formation, CD14-/- mice were able to clear B. fragilis more efficiently from the blood than CD14+/+ mice. After 3, 7, and 14 days blood cultures were B. fragilis positive in 11% (1/9), 20% (2/10), and 0% (0/9) in CD14-/-compared with 90% (9/10), 78% (7/9), and 20% (2/10) in CD14+/+ mice, respectively (P<0.05). Furthermore, although the infection resulted in hepatocellular necrosis and severe hepatitis in both groups, at day 14 the liver cell damage was more severe in CD14+/+ than in CD14-/- mice (P<0.05). These results show that the chronic abscess formation induced by B. fragilis capsular polysaccharides is CD14 independent; however, bacterial clearance and/or dissemination and liver cell damage are at least partially influenced by CD14-dependent mechanisms.

Recombinant bovine soluble CD14 reduces severity of experimental Escherichia coli mastitis in mice

“…Our finding of reduced mammary inflammation and reduced number of CFU in mice injected with rbosCD14 is partially supported by reports that CD14-deficient mice intraperitoneally challenged with E. coli [16] or Bacteroides fragilis [42] reduced dispersion of bacteria throughout the peritoneum. The authors proposed that monocytes in CD14-deficient mice were not activated by bacteria due to lack of mCD14, and this in turn reduced production of inflammatory cytokines, such as TNF-a and IL-1, which accelerate growth of bacteria [25,32].…”

Critical Role of CD14 for Production of Proinflammatory Cytokines and Cytokine Inhibitors during Sepsis with Failure To Alter Morbidity or Mortality

“…Previous studies using CD14KO mice have shown that the pathophysiology induced by Bacteroides does not require CD14 (53). This is partially due to the fact that the LPS from Bacteroides is at least 1,000 times less potent than LPS from Salmonella serovar Minnesota or E. coli (17).…”

“…This is partially due to the fact that the LPS from Bacteroides is at least 1,000 times less potent than LPS from Salmonella serovar Minnesota or E. coli (17). Furthermore, studies showing that the polysaccharide capsular components of Bacteroides induce disease (51) even in the absence of CD14 (53) suggest that the pathogenic effects seen in CLP may, in large part, be mediated by the non-LPS bacterial components of Bacteroides. Similarly, it has also previously been shown that sepsis induced by gram-positive bacteria shows very little, if any, dependence on CD14.…”

Recombinant Soluble CD14 Reduces Severity of Intramammary Infection byEscherichia coli

“…CD14-deficient mice were shown to have a delayed neutrophil influx in response to a peritoneal Salmonella challenge, which is associated with a reduced level of TNF-␣ (48). Contrarily, recruitment of neutrophils and bacterial clearance were enhanced in CD14 knockout mice intraperitoneally challenged with E. coli (16,18) or Bacteroides fragilis (45). The second approach was blockade of CD14.…”