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Increased susceptibility to Escherichia coli infection in mice pretreated with Corynebacterium parvum
Abstract:
The contribution of activated macrophages to protection against Escherichia coli was studied in mice treated intravenously with Corynebacterium parvum 7 days before infection. C. parvum-treated mice showed increased phagocytic activity and enhanced resistance to Listeria infection. In contrast, these mice showed increased susceptibility to a subsequent challenge with E. coli that correlated closely with a reduction in the LD50 of lipopolysaccharide (LPS) in these mice. The peritoneal macrophages obtained from C. parvum-treated mice had a strong ability to phagocytize and kill E. coli in in vitro experiments. A rapid decline in the number of bacteria in the liver of C. parvum-treated mice was observed in the early period of infection. However, the number of bacteria in liver and spleen increased progressively to a lethal dose from 6 hr after infection. At this time, a significant increase in beta-glucuronidase, a lysosomal acid hydrolase, was found in the serum of these mice. In vitro experiments revealed that the peritoneal macrophages from C. parvum-treated mice were highly susceptible to the cytotoxic effect of LPS after 6 hr of incubation with LPS. It is suggested that the hypersensitivity of activated macrophages to the cytotoxic effect of endotoxin derived from E. coli may be partly responsible for the increased susceptibility of C. parvum-treated mice to E. coli infection.
Insights
Corynebacterium parvum (C. parvum) activates macrophages, enhancing protection against Listeria but increasing susceptibility to Escherichia coli (E. coli) infection. This heightened E. coli susceptibility is linked to macrophage hypersensitivity to lipopolysaccharide (LPS).
Area of Science:
- Immunology
- Microbiology
Background:
- Activated macrophages play a crucial role in host defense against bacterial infections.
- Corynebacterium parvum (C. parvum) is known to activate macrophages, influencing immune responses.
Purpose of the Study:
- To investigate the role of activated macrophages in protection against Escherichia coli (E. coli) infection.
- To determine the effect of C. parvum treatment on macrophage function and susceptibility to E. coli.
Main Methods:
- Mice were treated with C. parvum intravenously 7 days before infection.
- Phagocytic activity and resistance to Listeria and E. coli infections were assessed.
- In vitro experiments evaluated peritoneal macrophage function and susceptibility to lipopolysaccharide (LPS).
- Bacterial counts in liver and spleen, and serum beta-glucuronidase levels were measured.
Main Results:
- C. parvum-treated mice showed enhanced resistance to Listeria but increased susceptibility to E. coli.
- Peritoneal macrophages from treated mice effectively phagocytosed and killed E. coli in vitro.
- Despite initial bacterial clearance, bacterial numbers increased significantly in treated mice after 6 hours.
- Macrophages from treated mice exhibited hypersensitivity to the cytotoxic effects of LPS in vitro.
Conclusions:
- Activated macrophages, while potent against some pathogens, can become hypersensitive to endotoxins like LPS.
- This macrophage hypersensitivity to E. coli-derived LPS may contribute to increased susceptibility to E. coli infection in C. parvum-treated mice.