Systemic activation of dendritic cells by Toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity

Nat. Immunol. 7, 165-172 (2006)

Speaker： 李羽涵                             Time：2006/05/17 13:10-14:00

Commentator：陳舜華 老師                    Place：Room 601

Abstract：

Dendritic cells (DCs) can present endogenous antigens to MHC class I molecule, which was called classical MHC class I presentation pathway. In addition to this pathway, DCs also have the capacity to deliver exogenous antigens to the MHC class I molecule, a phenomenon known as cross-presentation. Although cross-presentation underlies the ability to induce cytotoxic T lymphocyte (CTL) immunity (cross-priming) against tumor and cellular antigens, its function in viral immunity is debated. In this study, the authors used Toll-like receptor (TLR) ligands to mature CD8⁺ DC which were the most efficient subset at cross-presentation and then cultured with cellular-associated antigens and antigen-specific T cells. They found that matured DCs could not cross-present newly encountered cellular-associated antigens in vitro and in vivo. Furthermore, they used HSV to infect mice pretreated with TLR ligands and measured the presentation of HSV antigens. They observed the cross-presentation by matured DCs and CTL activity to virus was impaired. And matured DCs impaired at cross-presentation did not attributed to general suppression of T cells proliferation caused by TLR ligands pretreatment. Besides, they also found the mice infected with malaria, mimic a ‘real world’ condition for systemic DC activation, failed to cross-present antigen to CD8⁺ T cells. In a word, these findings demonstrated a mechanism likely to contribute to the immunosuppressive effects of sepsis or malaria infection and provided a rational approach for overcoming such suppression by treatments that bypass the processing requirements for cross-presentation.

References：

1.      Heath, W. R. et al. 2004. Cross-presentation dendritic cell subsets, and the generation of immunity to cellular antigens. Immunol. Rev. 199, 9-26.

2.      Wilson, N. S. et al. 2006. Systemic activation of dendritic cells by TLR ligans or malaria infection impairs cross-presentation and antiviral immunity. Nat. Immunol. 7, 165-172.