Role of germination in murine airway CD8+ T-cell responses to Aspergillus conidia
Steven P Templeton1, Amanda D Buskirk, Brandon Law
1Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia, United States of America. STempleton@cdc.gov
Abstract:
Pulmonary exposure to Aspergillus fumigatus has been associated with morbidity and mortality, particularly in immunocompromised individuals. A. fumigatus conidia produce β-glucan, proteases, and other immunostimulatory factors upon germination. Murine models have shown that the ability of A. fumigatus to germinate at physiological temperature may be an important factor that facilitates invasive disease. We observed a significant increase in IFN-γ-producing CD8(+) T cells in bronchoalveolar lavage fluid (BALF) of immunocompetent mice that repeatedly aspirated A. fumigatus conidia in contrast to mice challenged with A. versicolor, a species that is not typically associated with invasive, disseminated disease. Analysis of tissue sections indicated the presence of germinating spores in the lungs of mice challenged with A. fumigatus, but not A. versicolor. Airway IFN-γ(+)CD8(+) T-cells were decreased and lung germination was eliminated in mice that aspirated A. fumigatus conidia that were formaldehyde-fixed or heat-inactivated. Furthermore, A. fumigatus particles exhibited greater persistence in the lungs of recipient mice when compared to non-viable A. fumigatus or A. versicolor, and this correlated with increased maintenance of airway memory-phenotype CD8(+) T cells. Therefore, murine airway CD8(+) T cell-responses to aspiration of Aspergillus conidia may be mediated in part by the ability of conidia to germinate in the host lung tissue. These results provide further evidence of induction of immune responses to fungi based on their ability to invade host tissue.
Insights
Fungal germination in the lungs, particularly by Aspergillus fumigatus, drives immune responses and invasive disease. Preventing germination with inactivation methods reduces these T cell responses and fungal persistence.
Area of Science:
- Immunology
- Mycology
- Pulmonary Medicine
Background:
- Pulmonary exposure to Aspergillus fumigatus is linked to severe illness, especially in immunocompromised individuals.
- Aspergillus fumigatus conidia release immunostimulatory factors upon germination, and their ability to germinate at body temperature may facilitate invasive disease.
- CD8(+) T cells play a role in the immune response to fungal lung infections.
Purpose of the Study:
- To investigate the role of Aspergillus conidia germination in inducing pulmonary CD8(+) T cell responses.
- To compare the host response to Aspergillus fumigatus versus Aspergillus versicolor.
- To determine if inhibiting germination affects fungal persistence and immune cell responses.
Main Methods:
- Mice were repeatedly exposed to Aspergillus conidia via aspiration.
- Bronchoalveolar lavage fluid (BALF) and lung tissue sections were analyzed for immune cell populations and fungal presence.
- Aspergillus conidia were formaldehyde-fixed or heat-inactivated to assess the impact on germination and immune response.
- Fungal persistence in the lungs was quantified over time.
Main Results:
- Repeated aspiration of Aspergillus fumigatus, but not Aspergillus versicolor, led to increased IFN-γ-producing CD8(+) T cells in BALF and germinating spores in lung tissue.
- Inactivated Aspergillus fumigatus conidia significantly reduced airway IFN-γ(+)CD8(+) T cells and eliminated lung germination.
- Aspergillus fumigatus particles showed greater persistence in lungs compared to non-viable fungi or A. versicolor.
- Fungal persistence correlated with the maintenance of airway memory-phenotype CD8(+) T cells.
Conclusions:
- The ability of Aspergillus conidia to germinate in host lung tissue is a key factor in mediating murine airway CD8(+) T cell responses.
- Fungal germination and subsequent persistence are critical for the induction and maintenance of adaptive immune responses in the lungs.
- These findings highlight the importance of fungal viability and germination in the pathogenesis of invasive pulmonary aspergillosis.
