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- Title
Systemic activation of dendritic cells by Toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity.
- Authors
Wilson, Nicholas S.; Behrens, Georg M. N.; Lundie, Rachel J.; Smith, Christopher M.; Waithman, Jason; Young, Louise; Forehan, Simon P.; Mount, Adele; Steptoe, Raymond J.; Shortman, Ken D.; de Koning-Ward, Tania F.; Belz, Gabrielle T.; Carbone, Francis R.; Crabb, Brendan S.; Heath, William R.; Villadangos, Jose A.
- Abstract
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.
- Subjects
MALARIA; COMMUNICABLE diseases; IMMUNITY; DENDRITIC cells; CELL proliferation; VIRAL antigens; MAJOR histocompatibility complex
- Publication
Nature Immunology, 2006, Vol 7, Issue 2, p165
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni1300