Lactate Dehydrogenase-Elevating Virus Induces Systemic Lymphocyte Activation via TLR7-Dependent IFNα Responses by Plasmacytoid Dendritic CellsReportar como inadecuado




Lactate Dehydrogenase-Elevating Virus Induces Systemic Lymphocyte Activation via TLR7-Dependent IFNα Responses by Plasmacytoid Dendritic Cells - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Background

Lactate dehydrogenase-elevating virus LDV is a natural infectious agent of mice. Like several other viruses, LDV causes widespread and very rapid but transient activation of both B cells and T cells in lymphoid tissues and the blood. The mechanism of this activation has not been fully described and is the focus of the current studies.

Principal Findings

A known inducer of early lymphocyte activation is IFNα, a cytokine strongly induced by LDV infection. Neutralization of IFNα in the plasma from infected mice ablated its ability to activate lymphocytes in vitro. Since the primary source of virus-induced IFNα in vivo is often plasmacytoid dendritic cells pDC-s, we depleted these cells prior to LDV infection and tested for lymphocyte activation. Depletion of pDC-s in vivo eradicated both the LDV-induced IFNα response and lymphocyte activation. A primary receptor in pDC-s for single stranded RNA viruses such as LDV is the toll-like receptor 7 TLR7 pattern recognition receptor. Infection of TLR7-knockout mice revealed that both the IFNα response and lymphocyte activation were dependent on TLR7 signaling in vivo. Interestingly, virus levels in both TLR7 knockout mice and pDC-depleted mice were indistinguishable from controls indicating that LDV is largely resistant to the systemic IFNα response.

Conclusion

Results indicate that LDV-induced activation of lymphocytes is due to recognition of LDV nucleic acid by TLR7 pattern recognition receptors in pDC-s that respond with a lymphocyte-inducing IFNα response.



Autor: Christoph G. Ammann, Ronald J. Messer, Karin E. Peterson, Kim J. Hasenkrug

Fuente: http://plos.srce.hr/



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