TY - JOUR
T1 - Human and murine innate immune cell populations display common and distinct response patterns during their in vitro interaction with the pathogenic mold aspergillus fumigatu
AU - Hellmann, Anna Maria
AU - Lother, Jasmin
AU - Wurster, Sebastian
AU - Lutz, Manfred B.
AU - Schmitt, Anna Lena
AU - Morton, Charles Oliver
AU - Eyrich, Matthias
AU - Czakai, Kristin
AU - Einsele, Hermann
AU - Loeffler, Juergen
N1 - Publisher Copyright:
© 2017 Hellmann, Lother, Wurster, Lutz, Schmitt, Morton, Eyrich, Czakai, Einsele and Loeffler.
PY - 2017/12/6
Y1 - 2017/12/6
N2 - 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 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.
AB - 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 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.
KW - Aspergillus fumigatus
KW - Fungal infection
KW - Humans
KW - Innate immune response
KW - Murine model
UR - http://www.scopus.com/inward/record.url?scp=85037655205&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85037655205&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2017.01716
DO - 10.3389/fimmu.2017.01716
M3 - Article
C2 - 29270175
AN - SCOPUS:85037655205
SN - 1664-3224
VL - 8
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - DEC
M1 - 1716
ER -