A high mucosal blocking score is associated with HIV protection

被引:4
作者
Girard, Alexandre [1 ]
Rallon, Norma [2 ,3 ]
Benito, Jose M. [2 ,3 ]
Jospin, Fabienne [1 ]
Rodriguez, Carmen [3 ,4 ]
Chanut, Blandine [1 ]
Benjelloun, Fand [6 ]
Del Romero, Jorge [3 ,4 ]
Verrier, Bernard [5 ]
Lucht, Frederic [1 ]
Pin, Jean-Jacques [7 ]
Genin, Christian [1 ]
Biasin, Mara [8 ,9 ]
Clerici, Mario [8 ,9 ]
Paul, Stephane [1 ]
机构
[1] Univ Lyon, Univ St Etienne, GIMAP, EA 3064,CIC 1408, Lyon, France
[2] UAM, IIS Fdn Jimenez Diaz, Madrid, Spain
[3] Hosp Univ Rey Juan Carlos, Mostoles, Spain
[4] Ctr Sanitario Sandoval, Madrid, Spain
[5] Univ Lyon, FRE3310, Inst Biol & Chim Prot, CNRS, Lyon, France
[6] Inst Pasteur, Paris, France
[7] Dendritics, Lyon, France
[8] Univ Milan, Dept Physiopathol Med Surg & Transplantat, Milan, Italy
[9] IRCCS, Don C Gnocchi Fdn ONLUS, Milan, Italy
关键词
alpha; 4; beta; 7; DC-SIGN; gp120; highly exposed seronegative; langerin; mucosal blocking score; HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; EXPOSED SERONEGATIVE INDIVIDUALS; INTEGRIN ALPHA(4)BETA(7); DC-SIGN; DENDRITIC CELLS; ANTIBODIES; INFECTION; GP120; BINDING;
D O I
10.1097/QAD.0000000000002099
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: Early steps of HIV infection are mediated by the binding of the envelope to mucosal receptors as alpha 4 beta 7 and the C-type lectins DC-SIGN and langerin. Previously Env-specific B-cell responses have been reported in highly exposed seronegative individuals (HESN). Method: Here, we studied gp120-specific antibodies ability to block HIV interaction with alpha 4 beta 7, DC-SIGN and/or langerinin HESN. New cell-based assays were developed to analyze whether antibodies that can alter gp120 binding to alpha 4 beta 7, DC-SIGN and/or langerin are induced in HESN. A mucosal blocking score (MBS) was defined based on the ability of antibodies to interfere with gp120/alpha 4 beta 7, gp120/DC-SIGN, and gp120/langerin binding. A new MBS was evaluated in a cohort of 86 HESN individuals and compared with HIV thorn patients or HIV- unexposed healthy individuals. Results: Antibodies reducing gp120 binding to both alpha 4 beta 7 and DC-SIGN were present in HESN serum but also in mucosal secretions, whereas antibodies from HIV thorn patients facilitated gp120 binding to DC-SIGN. Any correlation was observed between MBS and the capacity of antibodies to neutralize infection of alpha 4 beta 7(+) CD4(+) T cells with primary isolates. Conclusions: MBS is significantly associated with protection in HESN and might reflect altered HIV spreading to mucosal-associated lymphoid tissues. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.
引用
收藏
页码:411 / 423
页数:13
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