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

Nat Immunol. 2006 Feb;7(2):165-72. doi: 10.1038/ni1300. Epub 2006 Jan 15.


The mechanisms responsible for the immunosuppression associated with sepsis or some chronic blood infections remain poorly understood. Here we show that infection with a malaria parasite (Plasmodium berghei) or simple systemic exposure to bacterial or viral Toll-like receptor ligands inhibited cross-priming. Reduced cross-priming was a consequence of downregulation of cross-presentation by activated dendritic cells due to systemic activation that did not otherwise globally inhibit T cell proliferation. Although activated dendritic cells retained their capacity to present viral antigens via the endogenous major histocompatibility complex class I processing pathway, antiviral responses were greatly impaired in mice exposed to Toll-like receptor ligands. This is consistent with a key function for cross-presentation in antiviral immunity and helps explain the immunosuppressive effects of systemic infection. Moreover, inhibition of cross-presentation was overcome by injection of dendritic cells bearing antigen, which provides a new strategy for generating immunity during immunosuppressive blood infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens, Viral
  • CpG Islands / immunology
  • Dendritic Cells / immunology*
  • Herpes Simplex / immunology
  • Herpesvirus 1, Human / immunology
  • Immune Tolerance
  • In Vitro Techniques
  • Ligands
  • Malaria / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Ovalbumin / immunology
  • Plasmodium berghei
  • T-Lymphocytes, Cytotoxic / immunology
  • Toll-Like Receptors / metabolism*


  • Antigens, Viral
  • Ligands
  • Toll-Like Receptors
  • Ovalbumin