Activation of human CD141+ and CD1c+ dendritic cells in vivo with combined TLR3 and TLR7/8 ligation

• DOI: 10.1111/imcb.12009
• Publication Date: 2018-01-18T09:01:37Z
• Authors: Frances E Pearson; Karshing Chang; Yoshihito Minoda; Ingrid M Leal Rojas; Oscar L Haigh; Ghazal Daraj; Kirsteen M Tullett; Kristen J Radford
• Keywords: TLR7

Mice reconstituted with human hematopoietic stem cells are valuable models to study aspects of the immune system in vivo. We describe a humanized mouse model (hu mice) which fully functional CD141+ and CD1c+ myeloid CD123+ plasmacytoid dendritic (DC) develop from cord blood CD34+ immunodeficient mice. DC equivalents murine CD8+ /CD103+ essential for induction tumor-inhibitory cytotoxic T lymphocyte responses, making them attractive targets exploit development new cancer immunotherapies. used -engrafted NSG-A2 mice investigate activation subsets by synthetic dsRNA or ssRNA analogs polyinosinic-polycytidylic acid/poly I:C Resiquimod/R848, agonists TLR3 TLR8, respectively, both expressed DC. Injection hu these resulted upregulation costimulatory molecules CD80, CD83 CD86 alike, their combination further enhanced expression subsets. When combined, poly R848 serum levels key cytokines associated cross-presentation responses including IFN-α, IFN-β, IL-12 CXCL10. These data advocate TLR as means activating immunotherapy.