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Updated: Aug 9, 2026
Whole Blood Assay with Dual Co-Stimulation for Antigen-Specific Analysis of Host Immunity to Fungal and Viral Pathogens
Published on: September 20, 2024
Immunomodulation with CD40 stimulation and interleukin-2 protects mice from disseminated cryptococcosis
Qing Zhou1, Ruth A Gault, Thomas R Kozel
1Department of Microbiology and Immunology, University of Nevada, Reno, 1664 N. Virginia St., Reno, NV 89557, USA.
Insights
Combination therapy with anti-CD40 and interleukin 2 (IL-2) significantly improved survival in a murine model of disseminated cryptococcosis. This antifungal efficacy was dependent on gamma interferon (IFN-γ).
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- Cryptococcus neoformans causes life-threatening infections in immunocompromised individuals.
- Current treatments for disseminated cryptococcosis have limitations.
Purpose of the Study:
- To investigate the antifungal efficacy of combining anti-CD40 agonist antibody with interleukin 2 (IL-2) in a murine model of disseminated cryptococcosis.
Main Methods:
- Mice with disseminated cryptococcosis were treated with anti-CD40 and IL-2 combination therapy.
- Survival rates, fungal burdens in organs, immune cell populations, and cytokine levels were assessed.
- Experiments included IFN-γ knockout mice and CD4+ T cell depletion.
Main Results:
- The combination of anti-CD40 and IL-2 significantly prolonged survival in infected mice.
- This protection correlated with reduced yeast burdens in the brain and kidneys.
- Treatment increased spleen immune cells, serum IFN-γ, and tumor necrosis factor alpha levels.
- Therapeutic efficacy was dependent on IFN-γ and not affected by CD4+ T cell depletion.
Conclusions:
- Immunotherapy with anti-CD40 and IL-2 shows therapeutic potential against disseminated cryptococcosis.
- IFN-γ is essential for the antifungal efficacy of this combination therapy.
Abstract:
Cryptococcus neoformans is a ubiquitous fungus that can cause life-threatening infections during immunosuppressive states such as AIDS and after bone marrow transplantation. In this study we investigated the antifungal efficacy of an agonist antibody to CD40, an important costimulator of immune function, in combination with interleukin 2 (IL-2) in a murine model of disseminated cryptococcosis. Only the combination of anti-CD40 and IL-2 significantly prolonged the survival time of infected mice. This protection was correlated with decreased yeast burdens in the brain and kidney. Increased immune cell populations in the spleens, as well as increased serum gamma interferon (IFN-gamma) and tumor necrosis factor alpha levels were observed in infected mice treated with anti-CD40 and IL-2. Further experiments with IFN-gamma knockout mice demonstrated that the protection induced by anti-CD40 and IL-2 treatment was dependent on IFN-gamma. Depletion of CD4+ T cells did not affect the increased serum IFN-gamma levels induced by anti-CD40 and IL-2 treatment and, importantly, did not affect the antifungal effect of combination therapy. These studies indicate that immunotherapy using anti-CD40 and IL-2 has therapeutic potential in augmenting host resistance to disseminated cryptococcosis and that IFN-gamma is essential for efficacy.
