Interplay of alphavirus-based replicons with dendritic cells induces innate immune activation and enhances adaptive immunity (53.1)
| Autor: | Daniel Tonkin, Mario Barro, Robert Johnston |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 188:53.1-53.1 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Venezuelan equine encephalitis virus replicon particles (VRP) are infectious, non-propagating particles which function as a safe and robust humoral, mucosal and cellular adjuvant when codelivered with antigen. VRP are known to infect dendritic cells (DCs) in vitro and in vivo, and we have explored the role of DCs in the adjuvant activity of VRP. Upon footpad injection VRP are rapidly transported to the draining lymph node, resulting in cytokine secretion and recruitment of leukocytes. We found that DCs were preferentially infected in the lymph node, although other cell types were also infected. TNF-secreting monocyte-derived inflammatory DCs were the cell type most dramatically recruited to the lymph node and also the most readily infected by VRP. These inflammatory DCs also efficiently took up antigen. By depletion of DCs we demonstrated that both VRP transport to the lymph node and the subsequent inflammatory response were at least partly DC-dependent. By in vitro analysis we found that VRP-infected DCs can amplify CD4 and CD8 T cell responses to antigen, which is mediated at least partly by DC-secreted factors. We also show that VRP-infected DCs are sufficient generate an adjuvant effect comparable to that achieved by injection of VRP alone. Altogether, these data provide strong evidence that in vivo targeting of DCs by VRP matures and alters those DCs in a manner that potentiates the adjuvant activity of VRP. |
| Databáze: | OpenAIRE |
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