TY  - JOUR
A1  - Hellmann, Anna-Maria
A1  - Lother, Jasmin
A1  - Wurster, Sebastian
A1  - Lutz, Manfred B.
A1  - Schmitt, Anna Lena
A1  - Morton, Charles Oliver
A1  - Eyrich, Matthias
A1  - Czakai, Kristin
A1  - Einsele, Hermann
A1  - Loeffler, Juergen
T1  - Human and Murine Innate Immune Cell Populations Display Common and Distinct Response Patterns during Their In Vitro Interaction with the Pathogenic Mold Aspergillus fumigatus
JF  - Frontiers in Immunology
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.
KW  - murine model
KW  - humans
KW  - Aspergillus fumigatus
KW  - innate immune response
KW  - fungal infection
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169926
VL  - 8
IS  - 1716
ER  - 
TY  - JOUR
A1  - Irmer, Henriette
A1  - Tarazona, Sonia
A1  - Sasse, Christoph
A1  - Olbermann, Patrick
A1  - Loeffler, Jürgen
A1  - Krappmann, Sven
A1  - Conesa, Ana
A1  - Braus, Gerhard H.
T1  - RNAseq analysis of Aspergillus fumigatus in blood reveals a just wait and see resting stage behavior
JF  - BMC Genomics
N2  - Background: 
Invasive aspergillosis is started after germination of Aspergillus fumigatus conidia that are inhaled by susceptible individuals. Fungal hyphae can grow in the lung through the epithelial tissue and disseminate hematogenously to invade into other organs. Low fungaemia indicates that fungal elements do not reside in the bloodstream for long.

Results: 
We analyzed whether blood represents a hostile environment to which the physiology of A. fumigatus has to adapt. An in vitro model of A. fumigatus infection was established by incubating mycelium in blood. Our model allowed to discern the changes of the gene expression profile of A. fumigatus at various stages of the infection. The majority of described virulence factors that are connected to pulmonary infections appeared not to be activated during the blood phase. Three active processes were identified that presumably help the fungus to survive the blood environment in an advanced phase of the infection: iron homeostasis, secondary metabolism, and the formation of detoxifying enzymes. 

Conclusions: 
We propose that A. fumigatus is hardly able to propagate in blood. After an early stage of sensing the environment, virtually all uptake mechanisms and energy-consuming metabolic pathways are shut-down. The fungus appears to adapt by trans-differentiation into a resting mycelial stage. This might reflect the harsh conditions in blood where A. fumigatus cannot take up sufficient nutrients to establish self-defense mechanisms combined with significant growth.
KW  - Saccharomyces cerevisiae
KW  - cerebral aspergillosis
KW  - gene expression
KW  - Aspergillus fumigatus
KW  - iron homeostasis
KW  - invasive pulmonary aspergillosis
KW  - Candida albicans
KW  - cell wall
KW  - lysine biosynthesis
KW  - human pathogen
KW  - murine model
KW  - virulence
KW  - mRNA-Seq
KW  - transcriptome
KW  - human pathogenic fungi
KW  - secondary metabolite gene cluster
KW  - detoxification
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151390
VL  - 16
IS  - 640
ER  -