Natural killer cell‐mediated contact dermatitis‐like reaction induced by treatment with TLR3 ligand poly(I:C)

Abstract

AbstractIntroductionPoly(I:C) is recognised by endosomal Toll‐like receptor 3 (TLR3) and activates cytotoxic CD8(+) lymphocytes and natural killer (NK) cells. It has been shown that the viral TLR3 agonist induces robust and long‐lasting T‐cell‐mediated responses. In addition, TLR3 modulates the contact hypersensitivity reaction.ObjectiveThis study aimed to determine whether poly(I:C) injection can induce NK‐mediated hapten reactivity in mice.MethodsMice were treated with poly(I:C), and their response to dinitrofluorobenzene hapten was measured by assessing ear swelling and serum interferon gamma (IFN‐γ) production. Adoptive cell transfer and cell sorting were used to investigate the mechanism of the reaction, and the phenotype of poly(I:C)‐activated liver NK cells was determined by flow cytometry analysis.ResultsThe results showed that poly(I:C) administration increased ear swelling, serum IFN‐γ levels and the response to hapten in both immunocompetent and T‐ and B‐cell‐deficient mice. Only liver poly(I:C)‐activated DX5(+) NK cells were able to transfer reactivity to hapten into a naive recipient. Induction of liver NK cells after poly(I:C) administration was TLR3/TRIF‐ and IFN‐γ‐dependent, interleukin 12‐independent, and not modulated by MyD88.ConclusionThis study provides new insights into how poly(I:C) stimulates NK‐mediated reactivity to hapten and suggests that liver NK cells may modulate the immune response to non‐pathogenic factors during viral infection.