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Impaired immune response to Candida albicans in aged mice
Celia Murciano1, Eva Villamón1, Alberto Yáñez1
1Departamento de Microbiología y Ecología, Universitat de València, Facultad de Ciencias Biológicas, Edificio de Investigación, C/Dr. Moliner 50, 46100 Burjasot, Valencia, Spain.
Abstract:
The prevalence of opportunistic fungal infections has increased dramatically among the aged population in recent years. This work investigated the effect of ageing on murine defences against Candida albicans. Aged C57BL/6 mice that were experimentally infected intravenously had a significantly impaired survival and a higher tissue fungal burden compared with young mice. In vitro production of tumour necrosis factor (TNF)-alpha by macrophages from aged mice in response to yeast cells and hyphae of C. albicans was significantly lower than production by macrophages from young mice. In vitro production of cytokines, such as TNF-alpha and gamma interferon (IFN-gamma), by antigen-stimulated splenocytes from mice intravenously infected with C. albicans cells was also diminished in old mice. This decrease in production of T helper 1 cytokines in old mice correlated with a diminished frequency of IFN-gamma-producing CD4+ T lymphocytes, although the ability to develop an acquired resistance upon vaccination (primary sublethal infection) of mice with the low-virulence PCA2 strain was not affected in aged mice. The diversity of antigens recognized by C. albicans-specific antibodies in sera from infected aged mice was clearly diminished when compared with that from infected young mice. Taken together, these data show that aged mice develop an altered innate and adaptive immune response to C. albicans and are more susceptible to systemic primary candidiasis.
Insights
Aging impairs immune defenses against Candida albicans infections. Older mice show reduced survival and higher fungal load due to weakened innate and adaptive immunity, increasing susceptibility to candidiasis.
Area of Science:
- Immunology
- Mycology
- Gerontology
Background:
- Opportunistic fungal infections, particularly Candida albicans, are increasing in the elderly.
- Age-related immune system decline (immunosenescence) impacts host defense mechanisms.
Purpose of the Study:
- To investigate the effects of aging on the host immune response to Candida albicans infection in mice.
- To compare the innate and adaptive immune capabilities of aged versus young mice against systemic candidiasis.
Main Methods:
- Intravenous experimental infection of aged and young C57BL/6 mice with Candida albicans.
- In vitro assessment of macrophage cytokine production (TNF-alpha) and splenocyte cytokine production (TNF-alpha, IFN-gamma).
- Analysis of CD4+ T lymphocyte frequency and antibody diversity in response to infection and vaccination.
Main Results:
- Aged mice exhibited significantly lower survival rates and higher fungal burdens post-infection compared to young mice.
- Macrophages from aged mice produced less tumor necrosis factor-alpha (TNF-alpha) in response to Candida albicans.
- Diminished production of T helper 1 cytokines (TNF-alpha, gamma interferon [IFN-gamma]) and reduced frequency of IFN-gamma-producing CD4+ T cells were observed in aged mice.
Conclusions:
- Aging alters both innate and adaptive immune responses to Candida albicans, rendering aged mice more susceptible to systemic candidiasis.
- Impaired cytokine production and T cell responses contribute to increased susceptibility in aged individuals.
- While primary resistance development was unaffected, overall immune defense against C. albicans is compromised with age.
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