Human and Murine Innate Immune Cell Populations Display Common and Distinct Response Patterns during Their In Vitro Interaction with the Pathogenic Mold Aspergillus fumigatus

Please always quote using this URN: urn:nbn:de:bvb:20-opus-169926
  • Aspergillus fumigatus is the main cause of invasive fungal infections occurring almost exclusively in immunocompromised patients. An improved understanding of the initial innate immune response is key to the development of better diagnostic tools and new treatment options. Mice are commonly used to study immune defense mechanisms during the infection of the mammalian host with A. fumigatus. However, little is known about functional differences between the human and murine immune response against this fungal pathogen. Thus, we performed aAspergillus fumigatus is the main cause of invasive fungal infections occurring almost exclusively in immunocompromised patients. An improved understanding of the initial innate immune response is key to the development of better diagnostic tools and new treatment options. Mice are commonly used to study immune defense mechanisms during the infection of the mammalian host with A. fumigatus. However, little is known about functional differences between the human and murine immune response against this fungal pathogen. Thus, we performed a comparative functional analysis of human and murine dendritic cells (DCs), macrophages, and polymorphonuclear cells (PMNs) using standardized and reproducible working conditions, laboratory protocols, and readout assays. A. fumigatus did not provoke identical responses in murine and human immune cells but rather initiated relatively specific responses. While human DCs showed a significantly stronger upregulation of their maturation markers and major histocompatibility complex molecules and phagocytosed A. fumigatus more efficiently compared to their murine counterparts, murine PMNs and macrophages exhibited a significantly stronger release of reactive oxygen species after exposure to A. fumigatus. For all studied cell types, human and murine samples differed in their cytokine response to conidia or germ tubes of A. fumigatus. Furthermore, Dectin-1 showed inverse expression patterns on human and murine DCs after fungal stimulation. These specific differences should be carefully considered and highlight potential limitations in the transferability of murine host–pathogen interaction studies.show moreshow less

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Metadaten
Author: Anna-Maria Hellmann, Jasmin Lother, Sebastian Wurster, Manfred B. Lutz, Anna Lena Schmitt, Charles Oliver Morton, Matthias Eyrich, Kristin Czakai, Hermann Einsele, Juergen Loeffler
URN:urn:nbn:de:bvb:20-opus-169926
Document Type:Journal article
Faculties:Medizinische Fakultät / Kinderklinik und Poliklinik
Medizinische Fakultät / Institut für Virologie und Immunbiologie
Medizinische Fakultät / Medizinische Klinik und Poliklinik II
Language:English
Parent Title (English):Frontiers in Immunology
Year of Completion:2017
Volume:8
Issue:1716
Source:Frontiers in Immunology 2017, Volume 8, Article 1716. DOI: 10.3389/fimmu.2017.01716
DOI:https://doi.org/10.3389/fimmu.2017.01716
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=29270175
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Aspergillus fumigatus; fungal infection; humans; innate immune response; murine model
Release Date:2019/09/04
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International