Capture of influenza by medullary dendritic cells via SIGN-R1 is essential for humoral immunity in draining lymph nodes

被引:194
作者
Gonzalez, Santiago F. [1 ,2 ,3 ,4 ]
Lukacs-Kornek, Veronika [5 ]
Kuligowski, Michael P. [1 ,2 ,3 ,4 ]
Pitcher, Lisa A. [1 ,2 ,3 ,4 ]
Degn, Soren E. [1 ,2 ,3 ,4 ,7 ]
Kim, Young-A [1 ,2 ,3 ,4 ]
Cloninger, Mary J. [6 ]
Martinez-Pomares, Luisa [8 ]
Gordon, Siamon [9 ]
Turley, Shannon J. [5 ]
Carroll, Michael C. [1 ,2 ,3 ,4 ]
机构
[1] Harvard Univ, Childrens Hosp, Immune Dis Inst, Sch Med,Dept Pediat, Boston, MA 02115 USA
[2] Harvard Univ, Childrens Hosp, Program Cellular & Mol Med, Sch Med,Dept Pediat, Boston, MA 02115 USA
[3] Harvard Univ, Childrens Hosp, Immune Dis Inst, Sch Med,Dept Pathol, Boston, MA 02115 USA
[4] Harvard Univ, Childrens Hosp, Program Cellular & Mol Med, Sch Med,Dept Pathol, Boston, MA 02115 USA
[5] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Pathol, Boston, MA 02115 USA
[6] Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA
[7] Aarhus Univ, Dept Med Microbiol & Immunol, Aarhus, Denmark
[8] Univ Nottingham, Sch Mol Med Sci, Nottingham NG7 2RD, England
[9] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
基金
美国国家卫生研究院;
关键词
ZONE B-CELLS; SUBCAPSULAR SINUS MACROPHAGES; MANNOSE-BINDING LECTIN; SPLENIC MARGINAL ZONE; IN-VIVO DEPLETION; CAPSULAR POLYSACCHARIDE; ANTIGEN PRESENTATION; ANTIBODY-RESPONSE; GERMINAL-CENTERS; MEDIATES UPTAKE;
D O I
10.1038/ni.1856
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
A major pathway for B cell acquisition of lymph-borne particulate antigens relies on antigen capture by subcapsular sinus macrophages of the lymph node. Here we tested whether this mechanism is also important for humoral immunity to inactivated influenza virus. By multiple approaches, including multiphoton intravital imaging, we found that antigen capture by sinus-lining macrophages was important for limiting the systemic spread of virus but not for the generation of influenza-specific humoral immunity. Instead, we found that dendritic cells residing in the lymph node medulla use the lectin receptor SIGN-R1 to capture lymph-borne influenza virus and promote humoral immunity. Thus, our results have important implications for the generation of durable humoral immunity to viral pathogens through vaccination.
引用
收藏
页码:427 / U90
页数:9
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