TY  - JOUR
A1  - Zoran, Tamara
A1  - Seelbinder, Bastian
A1  - White, Philip Lewis
A1  - Price, Jessica Sarah
A1  - Kraus, Sabrina
A1  - Kurzai, Oliver
A1  - Linde, Joerg
A1  - Häder, Antje
A1  - Loeffler, Claudia
A1  - Grigoleit, Goetz Ulrich
A1  - Einsele, Hermann
A1  - Panagiotou, Gianni
A1  - Loeffler, Juergen
A1  - Schäuble, Sascha
T1  - Molecular profiling reveals characteristic and decisive signatures in patients after allogeneic stem cell transplantation suffering from invasive pulmonary aspergillosis
JF  - Journal of Fungi
N2  - Despite available diagnostic tests and recent advances, diagnosis of pulmonary invasive aspergillosis (IPA) remains challenging. We performed a longitudinal case-control pilot study to identify host-specific, novel, and immune-relevant molecular candidates indicating IPA in patients post allogeneic stem cell transplantation (alloSCT). Supported by differential gene expression analysis of six relevant in vitro studies, we conducted RNA sequencing of three alloSCT patients categorized as probable IPA cases and their matched controls without Aspergillus infection (66 samples in total). We additionally performed immunoassay analysis for all patient samples to gain a multi-omics perspective. Profiling analysis suggested LGALS2, MMP1, IL-8, and caspase-3 as potential host molecular candidates indicating IPA in investigated alloSCT patients. MMP1, IL-8, and caspase-3 were evaluated further in alloSCT patients for their potential to differentiate possible IPA cases and patients suffering from COVID-19-associated pulmonary aspergillosis (CAPA) and appropriate control patients. Possible IPA cases showed differences in IL-8 and caspase-3 serum levels compared with matched controls. Furthermore, we observed significant differences in IL-8 and caspase-3 levels among CAPA patients compared with control patients. With our conceptual work, we demonstrate the potential value of considering the human immune response during Aspergillus infection to identify immune-relevant molecular candidates indicating IPA in alloSCT patients. These human host candidates together with already established fungal biomarkers might improve the accuracy of IPA diagnostic tools.
KW  - host response
KW  - invasive pulmonary aspergillosis
KW  - alloSCT patients
KW  - galectin-2
KW  - caspase-3
KW  - matrix metallopeptidase-1
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262105
SN  - 2309-608X
VL  - 8
IS  - 2
ER  - 
TY  - JOUR
A1  - Czakai, Kristin
A1  - Leonhardt, Ines
A1  - Dix, Andreas
A1  - Bonin, Michael
A1  - Linde, Joerg
A1  - Einsele, Hermann
A1  - Kurzai, Oliver
A1  - Loeffler, Jürgen
T1  - Krüppel-like Factor 4 modulates interleukin-6 release in human dendritic cells after in vitro stimulation with Aspergillus fumigatus and Candida albicans
JF  - Scientific Reports
N2  - Invasive fungal infections are associated with high mortality rates and are mostly caused by the opportunistic fungi Aspergillus fumigatus and Candida albicans. Immune responses against these fungi are still not fully understood. Dendritic cells (DCs) are crucial players in initiating innate and adaptive immune responses against fungal infections. The immunomodulatory effects of fungi were compared to the bacterial stimulus LPS to determine key players in the immune response to fungal infections. A genome wide study of the gene regulation of human monocyte-derived dendritic cells (DCs) confronted with A. fumigatus, C. albicans or LPS was performed and Krüppel-like factor 4 (KLF4) was identified as the only transcription factor that was down-regulated in DCs by both fungi but induced by stimulation with LPS. Downstream analysis demonstrated the influence of KLF4 on the interleukine-6 expression in human DCs. Furthermore, KLF4 regulation was shown to be dependent on pattern recognition receptor ligation. Therefore KLF4 was identified as a controlling element in the IL-6 immune response with a unique expression pattern comparing fungal and LPS stimulation.
KW  - gene regulation in immune cells
KW  - fungal host response
KW  - Aspergillus fumigatus
KW  - Candida albicans
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-181185
VL  - 6
ER  -