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Colony-stimulating factor 1-dependent resident macrophages play a regulatory role in fighting Escherichia coli fecal
W Wiktor-Jedrzejczak1, B Dzwigala, M Szperl
1Department of Immunology, Central Clinical Hospital, Military School of Medicine, Warsaw, Poland.
Abstract:
Osteopetrotic op/op mice have less than 5% of the normal number of macrophages in the peritoneal cavity (W. Wiktor-Jedrzejczak, A. Ahmed, C. Szczylik, and R.R. Skelly, J. Exp. Med. 156:1516-1527, 1982). Fecal peritonitis was induced by intraperitoneal injection of 0.5 ml of 5% autoclaved feces in saline along with Escherichia coli grown from feces of mice of the same colony and added in doses ranging between 10 and 10(6) CFU. Such infection led to a septic shock and either was lethal within 24 h or became cured without additional treatment of the mice. The op/op mice survived administration of 30-times-smaller doses of bacteria compared with their normal littermates. Analysis of the kinetics of cellular changes in the peritoneal cavity associated with such infection revealed that this increased susceptibility of macrophage-deficient mice cannot be explained by a direct role of macrophages in combating the infection. Instead, it appeared that the increased susceptibility to fatal fecal peritonitis was most likely due to delayed and impaired recruitment of neutrophils to the site of infection in mutant mice. The increased susceptibility of the op/op mice to E. coli fecal peritonitis was not due to their possible increased sensitivity to endotoxin, since the mutant mice tolerated lipopolysaccharide doses more than twice those tolerated by control littermates. On the other hand, their susceptibility to exogenous tumor necrosis factor alpha and interleukin-1 alpha was increased. Both mutant op/op and control mice were able to survive secondary challenge with 10(6) E. coli (administered along with feces) lethal for both types of mice on primary challenge. These data suggest that colony-stimulating factor 1-dependent resident peritoneal macrophages play a role in controlling primary infection by recruiting neutrophils and are not required for efficient response to secondary infection.
Insights
Osteopetrotic mice, lacking macrophages, show increased susceptibility to fecal peritonitis due to impaired neutrophil recruitment, not direct macrophage function in infection control.
Area of Science:
- Immunology
- Infectious Disease
- Genetics
Background:
- Osteopetrotic (op/op) mice exhibit a severe deficiency in resident peritoneal macrophages.
- Fecal peritonitis models are crucial for studying abdominal sepsis and host immune responses.
Purpose of the Study:
- To investigate the role of macrophages in the host defense against fecal peritonitis in op/op mice.
- To elucidate the mechanisms underlying increased susceptibility to infection in macrophage-deficient models.
Main Methods:
- Induction of fecal peritonitis in op/op and wild-type mice using feces and Escherichia coli.
- Analysis of peritoneal cellularity, including neutrophil recruitment kinetics.
- Assessment of susceptibility to endotoxin, tumor necrosis factor alpha, and interleukin-1 alpha.
Main Results:
- Op/op mice exhibited significantly higher mortality rates following primary bacterial challenge compared to controls.
- Increased susceptibility was attributed to delayed neutrophil recruitment, not a direct role of macrophages in combating infection.
- Op/op mice showed increased sensitivity to TNF-alpha and IL-1 alpha but not to LPS.
Conclusions:
- Resident peritoneal macrophages, dependent on colony-stimulating factor 1, are critical for initiating neutrophil recruitment during primary bacterial peritonitis.
- Macrophages are not essential for mounting an effective response to secondary infections in this model.