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Quantitative Imaging of Lineage-specific Toll-like Receptor-mediated Signaling in Monocytes and Dendritic Cells from Small Samples of Human Blood
Published on: April 16, 2012
Age-related defense against infection with intracellular pathogens
Abstract:
Young adult (6--12 weeks old) and aged (20--24 months old) NMRI mice were infected with various intracellular parasites. The following results were obtained: (1) After a sublethal infection with Listeria monocytogenes, aged mice were found to show a resistance similar to that of young adults. A challenge infection with this pathogen was followed by specific immunity of long duration in both age-groups. (2) On the other hand, young animals were significantly more resistant to Salmonella typhimurium than aged mice. It was concluded that this was due to the LD50 which was 14 times greater for 2-month-old than for 20-month-old mice. Furthermore, during 7 weeks after infection there were more S. typhimurium in the spleens of senescent mice than in those of young adult controls. (3) Aged mice showed highly increased susceptibility to the weakly virulent DX strain of Toxoplasma gondii. Almost all aged animals died whereas the control mice survived. When death of the aged mice was prevented by treatment with sulfadiazine after infection with the DX strain, the aged mice were found to be as well protected against subsequent infection with the strongly virulent BK strains as the young adult mice. These results suggest that the susceptibility of the aged animal to infectious agents may considerably vary from one pathogen to another.
Insights
Aging impacts immune responses to intracellular parasites differently. Aged mice showed similar resistance to Listeria monocytogenes but were more susceptible to Salmonella typhimurium and Toxoplasma gondii, indicating varied immune aging effects.
Area of Science:
- Immunology
- Gerontology
- Infectious Diseases
Background:
- Immune system function declines with age, increasing susceptibility to infections.
- The impact of aging on resistance to specific intracellular pathogens is not fully understood.
Purpose of the Study:
- To investigate age-related differences in immune responses to Listeria monocytogenes, Salmonella typhimurium, and Toxoplasma gondii.
- To determine if age affects the development of protective immunity after infection.
Main Methods:
- Young adult and aged mice were infected with L. monocytogenes, S. typhimurium, or T. gondii.
- Survival rates, LD50, and pathogen loads in spleens were assessed.
- Sulfadiazine treatment was used to assess T. gondii infection outcomes.
Main Results:
- Aged mice showed resistance to L. monocytogenes comparable to young adults, with long-lasting immunity.
- Young mice were significantly more resistant to S. typhimurium than aged mice, evidenced by higher LD50 and lower spleen bacterial loads.
- Aged mice exhibited high susceptibility to a weakly virulent T. gondii strain, with high mortality, but developed protective immunity after treatment.
Conclusions:
- Age-related susceptibility to intracellular parasites varies significantly.
- Immune aging does not uniformly impair all host defenses against infection.
- Specific pathogen characteristics and host immune responses dictate the outcome of aging on infectious disease resistance.
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