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Role of bacterial association with Kupffer cells in occurrence of endogenous systemic bacteremia
Y Hirakata1, K Tomono, K Tateda
1Department of Laboratory Medicine, Nagasaki University School of Medicine, Japan.
Abstract:
Bacteremia in immunocompromised hosts often arises from their endogenous intestinal flora. We produced experimental endogenous bacteremia by administering cyclophosphamide and ampicillin to conventional and specific-pathogen-free mice. The frequencies of bacteremia and mortality in the conventional mice were significantly higher than for the specific-pathogen-free mice. Pseudomonas aeruginosa was the major pathogen causing systemic bacteremia in conventional mice and was associated with a high mortality rate. Morganella morganii caused systemic bacteremia in both conventional and specific-pathogen-free mice. In contrast, Escherichia coli, enterococci, or other species most often caused portal bacteremia only. To determine the mechanism of occurrence of systemic bacteremia, we investigated bacterial blood clearance in mice and association with murine Kupffer cells, using several bacterial strains isolated from mice with bacteremia. Blood clearance rates and the abilities of isolated Kupffer cells to associate with bacteria were significantly greater for the organisms causing portal bacteremia than for those causing systemic bacteremia. There were no significant differences between the blood clearance rates in carrageenan-treated mice and that in normal mice. Moreover, association at 4 degrees C was not different from that at 37 degrees C. The results suggest that blood clearance of bacteria reflects bacterial adherence to Kupffer cells and that the resistance of bacteria to association with Kupffer cells plays an important role in the occurrence of overwhelming systemic bacteremia in this animal model.
Insights
Immunocompromised hosts are susceptible to bacteremia from gut bacteria. Bacterial resistance to Kupffer cell association significantly increases the risk of overwhelming systemic bacteremia in mice.
Area of Science:
- Microbiology
- Immunology
- Animal Models
Background:
- Bacteremia in immunocompromised individuals often originates from the gut microbiome.
- Understanding the mechanisms of systemic bacterial dissemination is crucial for managing infections in vulnerable populations.
Purpose of the Study:
- To investigate the factors contributing to systemic bacteremia in an experimental animal model.
- To elucidate the role of Kupffer cells and bacterial blood clearance in the pathogenesis of bacteremia.
Main Methods:
- Experimental bacteremia was induced in conventional and specific-pathogen-free mice using immunosuppressive agents (cyclophosphamide, ampicillin).
- Bacterial blood clearance and Kupffer cell association were assessed using various bacterial strains.
- Carrageenan treatment was used to investigate the role of Kupffer cells in bacterial clearance.
Main Results:
- Conventional mice exhibited higher rates of bacteremia and mortality compared to specific-pathogen-free mice.
- Pseudomonas aeruginosa and Morganella morganii were key pathogens in systemic bacteremia.
- Bacteria causing portal bacteremia showed higher blood clearance rates and Kupffer cell association than those causing systemic bacteremia.
- Bacterial adherence to Kupffer cells correlated with blood clearance rates, independent of temperature or carrageenan treatment.
Conclusions:
- Bacterial resistance to Kupffer cell association is a critical factor in the development of systemic bacteremia.
- Kupffer cell interaction plays a significant role in the host's ability to clear bacteria from the bloodstream.
- This animal model provides insights into the mechanisms underlying endogenous bacteremia in immunocompromised hosts.