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  - Lupiañez, Carmen B.
A1  - Villaescusa, Maria T.
A1  - Carvalho, Agostinho
A1  - Springer, Jan
A1  - Lackner, Michaela
A1  - Sánchez-Maldonado, José M.
A1  - Canet, Luz M.
A1  - Cunha, Cristina
A1  - Segura-Catena, Joana
A1  - Alcazar-Fuoli, Laura
A1  - Solano, Carlos
A1  - Fianchi, Luana
A1  - Pagano, Livio
A1  - Potenza, Leonardo
A1  - Aguado, José M.
A1  - Luppi, Mario
A1  - Cuenca-Estrella, Manuel
A1  - Lass-Flörl, Cornelia
A1  - Einsele, Hermann
A1  - Vázquez, Lourdes
A1  - Ríos-Tamayo, Rafael
A1  - Loeffler, Jürgen
A1  - Jurado, Manuel
A1  - Sainz, Juan
T1  - Common Genetic Polymorphisms within NF kappa B-Related Genes and the Risk of Developing Invasive Aspergillosis
JF  - Frontiers in Microbiology
N2  - Invasive Aspergillosis (IA) is an opportunistic infection caused by Aspergillus, a ubiquitously present airborne pathogenic mold. A growing number of studies suggest a major host genetic component in disease susceptibility. Here, we evaluated whether 14 single-nucleotide polymorphisms within NFκB1, NFκB2, RelA, RelB, Rel, and IRF4 genes influence the risk of IA in a population of 834 high-risk patients (157 IA and 677 non-IA) recruited through a collaborative effort involving the aspBIOmics consortium and four European clinical institutions. No significant overall associations between selected SNPs and the risk of IA were found in this large cohort. Although a hematopoietic stem cell transplantation (HSCT)-stratified analysis revealed that carriers of the IRF4rs12203592T/T genotype had a six-fold increased risk of developing the infection when compared with those carrying the C allele (ORREC = 6.24, 95%CI 1.25–31.2, P = 0.026), the association of this variant with IA risk did not reach significance at experiment-wide significant threshold. In addition, we found an association of the IRF4AATC and IRF4GGTC haplotypes (not including the IRF4rs12203592T risk allele) with a decreased risk of IA but the magnitude of the association was similar to the one observed in the single-SNP analysis, which indicated that the haplotypic effect on IA risk was likely due to the IRF4rs12203592 SNP. Finally, no evidence of significant interactions among the genetic markers tested and the risk of IA was found. These results suggest that the SNPs on the studied genes do not have a clinically relevant impact on the risk of developing IA.
KW  - Invasive Aspergillosis
KW  - genetic polymorphisms
KW  - susceptibility
KW  - NFkB-relatedgenes
KW  - interaction
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165209
VL  - 7
IS  - 1243
ER  -