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, N. S., Behrens, G. M. N., Lundie, R. J., Smith, C. M., Waithman, J., Young, L., Forehan, S. P., Mount, A., Steptoe, R. J., Shortman, K. D., de Koning-Ward, T. F., Belz, G. T., Carbone, F. R., Crabb, B. S., Heath, W. R. & Villadangos, J. A. (2006). Systemic activation of dendritic cells by Toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity. NATURE IMMUNOLOGY, 7 (2), pp.165-172. https://doi.org/10.1038/ni1300.
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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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