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Published on: December 11, 2013
Th1 and Th2 cytokine secretion patterns in murine candidiasis: association of Th1 responses with acquired resistance
Abstract:
Two chemically mutagenized agerminative variants of Candida albicans were used to immunize mice against challenge with highly virulent cells of the parent strain. Although both mutants (Vir- 3 and Vir- 13) resulted in nonlethal infection and could be recovered from mouse organs for many days after the intravenous inoculation of 10(7) to 10(6) cells, significant protection to systemic challenge with virulent C. albicans was induced by only one (Vir- 3) of the two variants. Anticandidal resistance in Vir- 3-infected mice was associated with the occurrence in vivo of strong delayed-type hypersensitivity to Candida antigen, detection in vitro of highly fungicidal effector macrophages, and presence in the serum of a large proportion of Candida-reactive antibodies of the immunoglobulin G2a isotype. Bulk cultures of purified CD4+ lymphocytes from mice infected with either mutant were compared for their ability to produce gamma interferon (IFN-gamma), interleukin-2 (IL-2), IL-4, and IL-6 in vitro. After stimulation with specific antigen, CD4+ cells from Vir- 3-immunized mice released large amounts of the Th1-specific cytokines, IFN-gamma and IL-2, at a time when CD4+ cells from Vir- 13-infected mice predominantly secreted the characteristic Th2 cytokines, IL-4 and IL-6. These results were confirmed by quantitative analysis of cytokine-producing Th1 and Th2 cells. In addition, only mice infected with Vir- 3 displayed a high frequency of CD8+ cells with the potential for in vitro lysis of yeast-primed bone marrow macrophages. Purified CD4+ cells from Vir- 3-infected mice, but not a mixture of these cells with CD4+ lymphocytes from mice infected with Vir- 13, could adoptively transfer delayed-type hypersensitivity reactivity onto naive mice. Taken together, these data suggest that both Th1 and Th2 CD4+ lymphocytes may be activated during experimental C. albicans infection in mice.
Insights
One Candida albicans mutant (Vir-3) induced significant protection against systemic infection in mice, linked to a Th1 immune response. The other mutant (Vir-13) induced a Th2 response, offering less protection.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Candida albicans is an opportunistic fungal pathogen causing systemic infections.
- Developing effective vaccines against C. albicans remains a challenge.
- Understanding the immune response to C. albicans infection is crucial for vaccine development.
Purpose of the Study:
- To investigate the protective immune responses induced by two agerminative Candida albicans mutants (Vir-3 and Vir-13) in a murine model.
- To compare the Th1/Th2 cytokine profiles and cellular immune mechanisms elicited by each mutant.
- To determine if these mutants can induce protective immunity against virulent C. albicans challenge.
Main Methods:
- Immunization of mice with chemically mutagenized, agerminative Candida albicans variants (Vir-3 and Vir-13).
- Challenge of immunized mice with virulent C. albicans and assessment of survival and protection.
- Analysis of cellular immunity, including delayed-type hypersensitivity, effector macrophage activity, and CD4+ and CD8+ T cell cytokine production (IFN-gamma, IL-2, IL-4, IL-6).
- Adoptive transfer of CD4+ T cells to assess their role in protective immunity.
Main Results:
- Only the Vir-3 mutant induced significant protection against systemic C. albicans challenge.
- Vir-3 immunization elicited a strong Th1 immune response characterized by high levels of IFN-gamma and IL-2, along with fungicidal macrophages and IgG2a antibodies.
- Vir-13 immunization induced a predominantly Th2 response with elevated IL-4 and IL-6, and less protection.
- CD4+ T cells from Vir-3-immunized mice transferred delayed-type hypersensitivity, while those from Vir-13 did not.
Conclusions:
- The Vir-3 mutant of Candida albicans can induce protective immunity through a Th1-biased immune response.
- The study highlights the importance of the Th1/Th2 balance in protective immunity against C. albicans.
- Both Th1 and Th2 CD4+ T cell subsets can be activated during experimental C. albicans infection.
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