Transcriptomic profiling of bovine blood dendritic cells and monocytes following TLR stimulation.

Barut, G. Tuba; Lischer, Heidi E. L.; Bruggmann, Rémy; Summerfield, Artur; Talker, Stephanie C. (2020). Transcriptomic profiling of bovine blood dendritic cells and monocytes following TLR stimulation. European journal of immunology, 50(11), pp. 1691-1711. Wiley-VCH 10.1002/eji.202048643

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Dendritic cells (DC) and monocytes are vital for the initiation of innate and adaptiveimmune responses. Recently, we identified bona fide DC subsets in blood of cattle, reveal-ing subset- and species-specific transcription of toll-like receptors (TLR). In the presentstudy, we analyzed phenotypic and transcriptional responses of bovine DC subsets andmonocytes to in vitro stimulation with four to six different TLR ligands. Bovine DC subsets,especially plasmacytoid DC (pDC), showed a clear increase of CCR7, CD25, CD40, CD80,CD86, and MHC-II expression both on mRNA and protein level. Flow cytometric detec-tion of p38 MAPK phosphorylation 15 min after stimulation confirmed activation of DCsubsets and monocytes in accordance with TLR gene expression. Whole-transcriptomesequencing of sorted and TLR-stimulated subsets revealed potential ligand- and subset-specific regulation of genes associated with inflammation, T-cell co-stimulation, migra-tion, metabolic reprogramming, and antiviral activity. Gardiquimod was found to evokestrong responses both in DC subsets and monocytes, while Poly(I:C) and CpG preferen-tially triggered responses in cDC1 and pDC, respectively. This in-depth analysis of ligandresponsiveness is essential for the rational design of vaccine adjuvants in cattle, and pro-vides a solid basis for comparative studies on DC and monocyte biology across species.

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