Systemic activation of dendritic cells by Toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity

被引:294
作者
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 [1 ]
Heath, WR
Villadangos, JA
机构
[1] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia
[2] Cooperat Res Ctr Vaccine Technol, Parkville, Vic 3050, Australia
[3] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia
[4] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia
[5] Univ Queensland, Ctr Immunol & Canc Res, Brisbane, Qld 4102, Australia
基金
英国惠康基金;
关键词
D O I
10.1038/ni1300
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:165 / 172
页数:8
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