Krüppel-like Factor 4 modulates interleukin-6 release in human dendritic cells after in vitro stimulation with Aspergillus fumigatus and Candida albicans.

Kristin Czakai,Hermann Einsele,Oliver Kurzai,Michael Bonin,Jürgen Loeffler,Joerg Linde,Ines Leonhardt,Andreas Dix

doi:10.1038/srep27990

Kristin Czakai, Hermann Einsele + Show 6 more

Open Access

https://doi.org/10.1038/srep27990

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Abstract

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.

Highlights

Activate or repress transcription, depending on the context[9]
Human Dendritic cells (DCs) were confronted with A. fumigatus, C. albicans and LPS, which was used as a standard control stimulus
Stimulation with LPS induced a differential regulation of 2793 genes after 6 h, while confrontation with A. fumigatus and C. albicans resulted in 743 and 1729 differentially regulated genes, respectively. 528 genes were regulated in all tested conditions after 6 h of co-cultivation (Fig. 1A)

Summary

Introduction

Activate or repress transcription, depending on the context[9]. In a murine system an influence of KLF4 on the Th2 response and on IL-6, a cytokine with pleiotropic functions and plays an important role in the transition from innate to acquired immunity and in promoting Th2 response was demonstrated[10,11,12]. We sought to analyse the possible regulatory role of KLF4 in the transition from innate to acquired immunity during fungal infections

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