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Course of primary candidiasis in T cell-depleted mice infected with attenuated variant cells
L Romani1, A Mencacci, E Cenci
1Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Abstract:
Anti-CD4, anti-CD8, or anti-interferon-gamma (IFN-gamma) antibodies or combinations of them were administered in the early stages of chronic infection of mice with a Candida albicans live vaccine strain, and the animals were monitored for course of primary infection, development of delayed-type hypersensitivity, resistance to reinfection, production of interleukin 2 (IL-2) and IFN-gamma in vitro by splenic lymphocytes, and levels of IL-2 and IFN-gamma transcripts in these cells. CD4+ cell and IFN-gamma depletion resulted in the development of fatal candidiasis by the attenuated yeast vaccine. In contrast, either treatment alone modified the course but not the outcome of primary infection, though each prevented the development of resistance to reinfection. Our data thus indicate that both IFN-gamma and CD4+ cells participate in resistance to primary infection with attenuated yeast cells and are critical in the induction of persistent systemic anticandidal immunity.
Insights
Depleting CD4+ cells and interferon-gamma (IFN-gamma) together leads to fatal candidiasis in mice. Both are crucial for immunity against Candida albicans and developing long-term resistance.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Candida albicans is an opportunistic fungal pathogen.
- Immune responses involving CD4+ T cells and interferon-gamma (IFN-gamma) are critical for controlling fungal infections.
Purpose of the Study:
- To investigate the roles of CD4+ cells and IFN-gamma in primary infection and acquired immunity against Candida albicans.
Main Methods:
- Mice with early chronic Candida albicans infection were treated with anti-CD4, anti-CD8, or anti-IFN-gamma antibodies.
- Evaluated infection course, delayed-type hypersensitivity, resistance to reinfection, and cytokine production (IL-2, IFN-gamma) by splenic lymphocytes.
- Assessed cytokine transcript levels in splenic lymphocytes.
Main Results:
- Combined depletion of CD4+ cells and IFN-gamma resulted in fatal candidiasis.
- Individual depletion modified infection course but not outcome, and impaired resistance to reinfection.
- Both CD4+ cells and IFN-gamma are essential for primary resistance and sustained anticandidal immunity.
Conclusions:
- CD4+ T cells and IFN-gamma play critical, cooperative roles in host defense against Candida albicans.
- These components are vital for establishing long-lasting systemic immunity following yeast infection.
- Targeting CD4+ cells or IFN-gamma pathways may impact the control of candidiasis.
