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  - 
TY  - JOUR
A1  - Ziegler, Sabrina
A1  - Weiss, Esther
A1  - Schmitt, Anna-Lena
A1  - Schlegel, Jan
A1  - Burgert, Anne
A1  - Terpitz, Ulrich
A1  - Sauer, Markus
A1  - Moretta, Lorenzo
A1  - Sivori, Simona
A1  - Leonhardt, Ines
A1  - Kurzai, Oliver
A1  - Einsele, Hermann
A1  - Loeffler, Juergen
T1  - CD56 Is a Pathogen Recognition Receptor on Human Natural Killer Cells
JF  - Scientific Reports
N2  - Aspergillus (A.) fumigatus is an opportunistic fungal mold inducing invasive aspergillosis (IA) in immunocompromised patients. Although antifungal activity of human natural killer (NK) cells was shown in previous studies, the underlying cellular mechanisms and pathogen recognition receptors (PRRs) are still unknown. Using flow cytometry we were able to show that the fluorescence positivity of the surface receptor CD56 significantly decreased upon fungal contact. To visualize the interaction site of NK cells and A. fumigatus we used SEM, CLSM and dSTORM techniques, which clearly demonstrated that NK cells directly interact with A. fumigatus via CD56 and that CD56 is re-organized and accumulated at this interaction site time-dependently. The inhibition of the cytoskeleton showed that the receptor re-organization was an active process dependent on actin re-arrangements. Furthermore, we could show that CD56 plays a role in the fungus mediated NK cell activation, since blocking of CD56 surface receptor reduced fungal mediated NK cell activation and reduced cytokine secretion. These results confirmed the direct interaction of NK cells and A. fumigatus, leading to the conclusion that CD56 is a pathogen recognition receptor. These findings give new insights into the functional role of CD56 in the pathogen recognition during the innate immune response.
KW  - pattern recognition receptors
KW  - fungal infection
KW  - Aspergillus fumigatus
KW  - natural killer cells
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170637
VL  - 7
IS  - 6138
ER  -