TY - JOUR AU - Wilson, NS AU - Behrens, GMN AU - Lundie, RJ AU - Smith, CM AU - Waithman, J AU - Young, L AU - Forehan, SP AU - Mount, A AU - Steptoe, RJ AU - Shortman, KD AU - de Koning-Ward, TF AU - Belz, GT AU - Carbone, FR AU - Crabb, BS AU - Heath, WR AU - Villadangos, JA Y2 - 2014/05/21 Y2 - 2005/12/09 Y2 - 2005/12/09 Y2 - 2005/12/09 Y2 - 2005/12/09 Y2 - 2005/12/09 Y2 - 2005/12/09 Y2 - 2005/12/09 Y2 - 2005/12/09 Y2 - 2005/12/09 Y1 - 2006/02/01 SN - 1529-2908 UR - http://hdl.handle.net/11343/26245 AB - 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. N1 - application/pdf LA - English PB - NATURE PUBLISHING GROUP KW - Cellular Immunology; Immune System and Allergy T1 - Systemic activation of dendritic cells by Toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity DO - 10.1038/ni1300 IS - NATURE IMMUNOLOGY VL - 7 IS - 2 SP - 165-172 L1 - /bitstream/handle/11343/26245/116017_5069.pdf?sequence=1&isAllowed=n ER -