Systemic activation of dendritic cells by Toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity
AuthorWilson, NS; Behrens, GMN; Lundie, RJ; Smith, CM; Waithman, J; Young, L; Forehan, SP; Mount, A; Steptoe, RJ; Shortman, KD; ...
Source TitleNATURE IMMUNOLOGY
PublisherNATURE PUBLISHING GROUP
University of Melbourne Author/sCarbone, Francis; Crabb, Brendan; Shortman, Kenneth; Belz, Gabrielle; Villadangos, Jose; Heath, William; WILSON, NICHOLAS STUART; WAITHMAN, JASON CHRISTOPHER; DE KONING-WARD, TANIA FRANCES
AffiliationMicrobiology And Immunology
Document TypeJournal Article
CitationsWilson, 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, Systemic activation of dendritic cells by Toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity, NATURE IMMUNOLOGY, 2006, 7 (2), pp. 165 - 172
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C1 - Journal Articles Refereed
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.
KeywordsCellular Immunology; Immune System and Allergy
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