Vreman Sandra, Auray Gael, Savelkoul Huub F J, Rebel Annemarie, Summerfield Artur, Stockhofe-Zurwieden Norbert
Wageningen Bioveterinary Research, Wageningen University & Research, P.O. Box 29703, 2502 LS, The Hague, The Netherlands.
Institute of Virology and Immunology, Sensemattstrasse 293, 3147, Mittelhausern, Switzerland; Department of Infectious Diseases and Pathobiology, University of Bern, Switzerland.
Dev Comp Immunol. 2018 Jul;84:361-370. doi: 10.1016/j.dci.2018.03.012. Epub 2018 Mar 17.
The present study investigated the innate immune response in vitro to determine porcine neonate responses with Toll-like receptor (TLR)2 ligand (Pam3Cys) or TLR9 ligand (CpG) and compared these with adults. We identified the same phenotypically defined dendritic cell (DC) subsets and DC proportions in porcine neonate and adult blood by flow cytometry, which were plasmacytoid DCs (pDCs): CD14CD4CD172aCADM1) and conventional DCs (cDCs), being further divided into a cDC1 (CD14CD4CD172aCADM1) and a cDC2 (CD14CD4CD172aCADM1) subset. With neonatal cells, the TLR2 ligand induced a stronger TNF expression in monocytes and pDCs, and a stronger CD80/86 upregulation in cDC1, when compared to adult cells. Furthermore, in neonatal mononuclear cells TLR9 ligand was more potent at inducing IL12p40 mRNA expression. These results indicate clear responses of porcine neonatal antigen presenting cells after TLR2 and TLR9 stimulation, suggesting that corresponding ligands could be promising candidates for neonatal adjuvant application.
本研究在体外研究了天然免疫反应,以确定猪新生儿对Toll样受体(TLR)2配体(Pam3Cys)或TLR9配体(CpG)的反应,并将这些反应与成年猪进行比较。我们通过流式细胞术在猪新生儿和成年猪血液中鉴定出了表型定义相同的树突状细胞(DC)亚群和DC比例,即浆细胞样DC(pDC):CD14CD4CD172aCADM1)和传统DC(cDC),后者进一步分为cDC1(CD14CD4CD172aCADM1)和cDC2(CD14CD4CD172aCADM1)亚群。与成年细胞相比,对于新生儿细胞,TLR2配体在单核细胞和pDC中诱导更强的TNF表达,在cDC1中诱导更强的CD80/86上调。此外,在新生儿单核细胞中,TLR9配体在诱导IL12p40 mRNA表达方面更有效。这些结果表明,TLR2和TLR9刺激后猪新生儿抗原呈递细胞有明显反应,提示相应配体可能是新生儿佐剂应用的有前景的候选物。