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Aspergillus fumigatus conidia induce a Th1-type cytokine response
M L Grazziutti1, J H Rex, R E Cowart
1Department of Internal Medicine, Center for the Study of Emerging and Reemerging Pathogens, University of Texas Medical School, Houston, USA.
Abstract:
The response of human peripheral blood mononuclear cells (MNC) to Aspergillus fumigatus in vitro was evaluated. In studies of the proliferative response of MNC from 18 healthy donors to heat-killed A. fumigatus conidia, 15 displayed a significant response, with a stimulation index (SI) between 4 and 193. In contrast, all donors displayed a positive response to Candida albicans blastoconidia (SI ranged from 10 to 224). Despite the variability in reactivity to A. fumigatus conidia, the response of a particular individual was stable when retested over periods of 1-2 weeks. Supernatant from cocultures of A. fumigatus conidia with MNC contained increased levels of interferon-gamma, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interleukin (IL)-2, compared with unstimulated cells, but not IL-10 or IL-4. In addition, A. fumigatus induced lymphocyte surface expression of adhesion/activation-associated molecules. These results suggest that lymphocytes may contribute to host defense against Aspergillus by generating a Th1-type response.
Insights
Human peripheral blood mononuclear cells (MNC) show a significant in vitro response to Aspergillus fumigatus, indicating a potential Th1-type immune response. This cellular reactivity to fungal pathogens is stable over time.
Area of Science:
- Immunology
- Microbiology
Background:
- Human peripheral blood mononuclear cells (MNC) are crucial for immune responses.
- Aspergillus fumigatus is an opportunistic fungal pathogen.
- Understanding immune responses to fungal infections is vital for developing treatments.
Purpose of the Study:
- To evaluate the in vitro immune response of human MNC to Aspergillus fumigatus.
- To characterize the type of immune response generated against A. fumigatus.
Main Methods:
- Proliferative assays using MNC from healthy donors stimulated with heat-killed A. fumigatus conidia.
- Measurement of cytokine levels (interferon-gamma, GM-CSF, TNF-alpha, IL-2, IL-10, IL-4) in coculture supernatants.
- Analysis of lymphocyte surface molecule expression.
Main Results:
- A significant proliferative response to A. fumigatus was observed in 15 out of 18 donors.
- Cytokine analysis revealed increased levels of Th1-associated cytokines (IFN-gamma, TNF-alpha, IL-2) but not Th2 cytokines (IL-4, IL-10).
- A. fumigatus induced the expression of adhesion/activation molecules on lymphocytes.
Conclusions:
- Human MNC mount a Th1-type immune response against Aspergillus fumigatus.
- Lymphocytes play a role in host defense against Aspergillus infections.
- The observed immune response is specific and stable in individuals.