Systemic activation of dendritic cells by Toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity
- Author(s)
- Wilson, NS; Behrens, GMN; Lundie, RJ; Smith, CM; Waithman, J; Young, L; Forehan, SP; Mount, A; Steptoe, RJ; Shortman, KD; de Koning-Ward, TF; Belz, GT; Carbone, FR; Crabb, BS; Heath, WR; Villadangos, JA;
- Details
- Publication Year 2006-02,Volume 7,Issue #2,Page 165-172
- Journal Title
- NATURE IMMUNOLOGY
- Publication Type
- Journal Article
- 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.
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- HERPES-SIMPLEX VIRUS; IN-VIVO; ANTIGEN PRESENTATION; LANGERHANS CELLS; CUTTING EDGE; POSITIVE SELECTION; TRANSGENIC MOUSE; LIFE-CYCLE; T-CELLS; EXPRESSION
- Publisher's Version
- https://doi.org/10.1038/ni1300
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2006-02-01 12:00:00