Frequency of IRF5+ dendritic cells is associated with the TLR7-induced inflammatory cytokine response in SARS-CoV-2 infection
The SARS-CoV-2 infection leads to enhanced inflammation driven by innate immune responses. Upon TLR7 stimulation, dendritic cells (DC) mediate the production of inflammatory cytokines, and in particular of type I interferons (IFN). Especially in DCs, IRF5 is a key transcription factor that regulates...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
February 2023
|
| In: |
Cytokine
Year: 2023, Volume: 162, Pages: 1-9 |
| ISSN: | 1096-0023 |
| DOI: | 10.1016/j.cyto.2022.156109 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.cyto.2022.156109 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1043466622003180 
|
| Author Notes: | Leon Cords, Robin Woost, Silke Kummer, Thomas T. Brehm, Stefan Kluge, Stefan Schmiedel, Sabine Jordan, Ansgar W. Lohse, Marcus Altfeld, Marylyn M. Addo, Julian Schulze zur Wiesch, Claudia Beisel |
| Summary: | The SARS-CoV-2 infection leads to enhanced inflammation driven by innate immune responses. Upon TLR7 stimulation, dendritic cells (DC) mediate the production of inflammatory cytokines, and in particular of type I interferons (IFN). Especially in DCs, IRF5 is a key transcription factor that regulates pathogen-induced immune responses via activation of the MyD88-dependent TLR signaling pathway. In the current study, the frequencies of IRF5+ DCs and the association with innate cytokine responses in SARS-CoV-2 infected individuals with different disease courses were investigated. In addition to a decreased number of mDC and pDC subsets, we could show reduced relative IRF5+ frequencies in mDCs of SARS-CoV-2 infected individuals compared with healthy donors. Functionally, mDCs of COVID-19 patients produced lower levels of IL-6 in response to in vitro TLR7 stimulation. IRF5+ mDCs more frequently produced IL-6 and TNF-α compared to their IRF5− counterparts upon TLR7 ligation. The correlation of IRF5+ mDCs with the frequencies of IL-6 and TNF-α producing mDCs were indicators for a role of IRF5 in the regulation of cytokine responses in mDCs. In conclusion, our data provide further insights into the underlying mechanisms of TLR7-dependent immune dysfunction and identify IRF5 as a potential immunomodulatory target in SARS-CoV-2 infection. |
|---|---|
| Item Description: | Published: 13 December 2022 Gesehen am 13.06.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1096-0023 |
| DOI: | 10.1016/j.cyto.2022.156109 |