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Susceptibility of HRS/J mice to listeriosis: macrophage activity
1Department of Microbiology, University of Massachusetts, Amherst 01003.
Abstract:
Macrophage functions, including phagocytosis and bactericidal and oxidative activities, were measured in highly susceptible Listeria monocytogenes-sensitive HRS/J homozygous and heterozygous mice. Phagocytic studies with both caseinate-elicited and L. monocytogenes-immune macrophages revealed comparable engulfment of latex particles, zymosan, and bacteria by mononuclear phagocytes obtained from all experimental mouse strains. Elicited macrophages cultivated from mutant hairless and heterozygous littermates exhibited a reduced capacity to control Listeria infection compared with cells derived from CD-1 mice. However, intracellular killing of the microorganisms by immune macrophages was comparable to that observed with the outbred controls. Studies on oxidative metabolic activities associated with the respiratory burst indicate that while intracellular nitroblue tetrazolium reduction was comparable for macrophages cultivated from all mouse strains, the liberation of superoxide anion and chemiluminescence responses were significantly diminished in caseinate-elicited HRS/J cells. Moreover, immune elicited hr/hr and hr/+ macrophages generated oxidative species at levels comparable to that observed with cells derived from resistant animals. Thus, immunologically elicited HRS/J mice are capable of responding to sublethal Listeria infection with heightened antibacterial and oxidative activities.
Insights
Mice with a specific genetic mutation (HRS/J) showed reduced control over Listeria monocytogenes infection due to impaired macrophage oxidative activity. However, immune responses in these mice enhanced their ability to fight the bacteria.
Area of Science:
- Immunology
- Microbiology
- Genetics
Background:
- Macrophage dysfunction can lead to increased susceptibility to infections.
- The HRS/J mouse strain exhibits high susceptibility to Listeria monocytogenes.
- Understanding macrophage function in HRS/J mice is crucial for deciphering host-pathogen interactions.
Purpose of the Study:
- To investigate macrophage functions, including phagocytosis, bactericidal activity, and oxidative burst, in Listeria monocytogenes-sensitive HRS/J mice.
- To compare the immune responses of HRS/J mice with control strains (CD-1 mice).
- To determine the role of oxidative metabolic activities in the susceptibility of HRS/J mice.
Main Methods:
- Macrophage functions were assessed in caseinate-elicited and Listeria monocytogenes-immune macrophages from HRS/J (homozygous and heterozygous) and CD-1 mice.
- Phagocytosis was measured using latex particles, zymosan, and Listeria monocytogenes.
- Bactericidal activity and oxidative burst (nitroblue tetrazolium reduction, superoxide anion liberation, chemiluminescence) were quantified.
Main Results:
- Phagocytic capacity was comparable across all mouse strains.
- Elicited HRS/J macrophages showed reduced control over Listeria infection compared to CD-1 mice.
- While intracellular killing was similar, oxidative burst responses (superoxide anion, chemiluminescence) were diminished in elicited HRS/J macrophages.
- Immune-elicited HRS/J macrophages exhibited comparable oxidative species generation to resistant animals.
Conclusions:
- HRS/J mice possess macrophages with impaired oxidative burst activity, contributing to their susceptibility to Listeria monocytogenes.
- Despite reduced oxidative capacity, immune stimulation enhances the antibacterial and oxidative activities of HRS/J macrophages.
- These findings highlight the complex interplay between genetic background, macrophage function, and host defense against bacterial infections.