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Relationship between age and cellular suppressive activity in resistance to Histoplasma capsulatum infection
Abstract:
One-month-old and 1-year-old male BALB/c mice showed a lower resistance than 4.5-month-old mice to Histoplasma capsulatum infection. 4.5-month-old mice successfully resolved the infection when challenged with either a LD50 or LD100 for 1-month-old mice. A critical clinical course of experimental histoplasmosis was observed in 4.5-month-old syngeneic mice when spleen cells from 1-month-old BALB/c mice were transferred to them. Irradiated recipient mice, into which bone marrow and spleen cells were transferred, died when infected with the LD100 for 1-month-old mice. The same occurred with 4.5-month-old non-irradiated infected mice which received only spleen cells and with 1-month-old mice which were used as a control of infection. However, infected and non-transferred 4.5-month-old mice survived this dose. Thus, the adoptive transference of spleen cells from 1-month-old mice to 4.5-month-old mice suppressed the resistance of these adult mice to infection. Apparently, the transference of the suppressive state requires the presence of two cell populations, a non-adherent and an adherent and radioresistant cell present in the spleen of male 1-month-old mice.
Insights
Young BALB/c mice spleen cells transfer suppressed adult mice resistance to Histoplasma capsulatum infection. This indicates a transferable suppressive state mediated by specific cell populations.
Area of Science:
- Immunology
- Infectious Diseases
- Microbiology
Background:
- Age significantly impacts BALB/c mice resistance to Histoplasma capsulatum.
- Younger mice (1-month-old) exhibit lower resistance compared to adult mice (4.5-month-old).
Purpose of the Study:
- To investigate the immunological mechanisms underlying age-dependent resistance to Histoplasma capsulatum.
- To determine if the reduced resistance in young mice is transferable to adult mice.
Main Methods:
- Comparative infection studies using BALB/c mice of different ages (1-month, 4.5-month, and 1-year-old).
- Adoptive transfer of spleen cells from young (1-month-old) to adult (4.5-month-old) syngeneic mice.
- Infection challenge with varying doses (LD50, LD100) of Histoplasma capsulatum.
- Evaluation of survival rates and clinical course in recipient mice.
Main Results:
- 4.5-month-old mice normally resolved Histoplasma capsulatum infection.
- Adoptive transfer of spleen cells from 1-month-old mice to 4.5-month-old mice resulted in a critical clinical course and mortality.
- Irradiated mice receiving bone marrow and spleen cells from young mice succumbed to infection.
- Non-irradiated adult mice receiving only spleen cells from young mice also showed suppressed resistance.
- The suppressive state appears to require both non-adherent and adherent, radioresistant spleen cell populations from young mice.
Conclusions:
- Spleen cells from young mice transfer a suppressive state that abrogates the natural resistance of adult mice to Histoplasma capsulatum.
- This age-related immune suppression is mediated by specific cell populations within the spleen.
- Findings suggest a complex interplay of cellular immunity and age in controlling fungal infections.