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Cytokine induction in human coccidioidomycosis
D P Dooley1, R A Cox, K L Hestilow
1Department of Research Immunology, Texas Center for Infectious Disease, San Antonio 78223-3597.
Infection and Immunity
|September 1, 1994
Summary
This study shows that immune cells from individuals with Coccidioides immitis infection and healthy individuals produce inflammatory cytokines when exposed to the fungus. This cytokine production may drive disease and vaccine side effects.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- Coccidioides immitis causes coccidioidomycosis, a significant fungal infection.
- Understanding the immune response is crucial for managing the disease and developing effective treatments.
Purpose of the Study:
- To investigate the cytokine production by immune cells in response to Coccidioides immitis.
- To compare immune responses in healthy individuals and those with active coccidioidomycosis.
Main Methods:
- Peripheral blood mononuclear cells (PBMC) and monocytes/macrophages (Mphi) were isolated from three groups: healthy skin test positive, healthy skin test negative, and patients with active coccidioidomycosis.
- Cytokine levels (TNF-alpha, IL-1 beta, IL-6) were measured using enzyme-linked immunosorbent assays (ELISA) after stimulation with formalin-killed spherules (FKS) and viable C. immitis.
Main Results:
- PBMC and Mphi from all donor groups secreted increased levels of TNF-alpha, IL-1 beta, and IL-6 in response to FKS stimulation.
- Viable C. immitis also stimulated cytokine production, but at lower levels than FKS.
- Elevated cytokine production was observed across healthy and infected individuals.
Conclusions:
- The production of acute inflammatory cytokines like TNF-alpha, IL-1 beta, and IL-6 may contribute to the immunopathogenesis of active coccidioidomycosis.
- This cytokine response could explain the observed toxicity of the FKS vaccine in humans.