Dynamic Immune Cell Recruitment After Murine Pulmonary Aspergillus fumigatus Infection under Different Immunosuppressive Regimens
Please always quote using this URN: urn:nbn:de:bvb:20-opus-165368
- Humans are continuously exposed to airborne spores of the saprophytic fungus Aspergillus fumigatus. However, in healthy individuals pulmonary host defense mechanisms efficiently eliminate the fungus. In contrast, A. fumigatus causes devastating infections in immunocompromised patients. Host immune responses against A. fumigatus lung infections in immunocompromised conditions have remained largely elusive. Given the dynamic changes in immune cell subsets within tissues upon immunosuppressive therapy, we dissected the spatiotemporal pulmonaryHumans are continuously exposed to airborne spores of the saprophytic fungus Aspergillus fumigatus. However, in healthy individuals pulmonary host defense mechanisms efficiently eliminate the fungus. In contrast, A. fumigatus causes devastating infections in immunocompromised patients. Host immune responses against A. fumigatus lung infections in immunocompromised conditions have remained largely elusive. Given the dynamic changes in immune cell subsets within tissues upon immunosuppressive therapy, we dissected the spatiotemporal pulmonary immune response after A. fumigatus infection to reveal basic immunological events that fail to effectively control invasive fungal disease. In different immunocompromised murine models, myeloid, notably neutrophils, and macrophages, but not lymphoid cells were strongly recruited to the lungs upon infection. Other myeloid cells, particularly dendritic cells and monocytes, were only recruited to lungs of corticosteroid treated mice, which developed a strong pulmonary inflammation after infection. Lymphoid cells, particularly CD4\(^+\) or CD8\(^+\) T-cells and NK cells were highly reduced upon immunosuppression and not recruited after A. fumigatus infection. Moreover, adoptive CD11b\(^+\) myeloid cell transfer rescued cyclophosphamide immunosuppressed mice from lethal A. fumigatus infection but not cortisone and cyclophosphamide immunosuppressed mice. Our findings illustrate that CD11b\(^+\) myeloid cells are critical for anti-A. fumigatus defense under cyclophosphamide immunosuppressed conditions.…
Author: | Natarajaswamy Kalleda, Jorge Amich, Berkan Arslan, Spoorthi Poreddy, Katharina Mattenheimer, Zeinab Mokhtari, Hermann Einsele, Matthias Brock, Katrin Gertrud Heinze, Andreas Beilhack |
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URN: | urn:nbn:de:bvb:20-opus-165368 |
Document Type: | Journal article |
Faculties: | Graduate Schools / Graduate School of Life Sciences |
Medizinische Fakultät / Medizinische Klinik und Poliklinik II | |
Fakultät für Biologie / Rudolf-Virchow-Zentrum | |
Language: | English |
Parent Title (English): | Frontiers in Microbiology |
Year of Completion: | 2016 |
Volume: | 7 |
Issue: | 1107 |
Source: | Frontiers in Microbiology 2016 7:1107. doi: 10.3389/fmicb.2016.01107 |
DOI: | https://doi.org/10.3389/fmicb.2016.01107 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | CD11b+ myeloid cells; aspergillus fumigatus; corticosteroids and cyclophosphamide; immune cell recruitment |
Release Date: | 2018/10/21 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |