The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity

被引：1

作者：

Marin-Lopez, Alejandro ^{[1
]}

Huck, John D. ^{[2
]}

Esterly, Allen T. ^{[3
]}

Azcutia, Veronica ^{[4
,7
]}

Rosen, Connor ^{[2
,8
]}

Garcia-Milian, Rolando ^{[5
]}

Sefik, Esen ^{[2
]}

Vidal-Pedrola, Gemma ^{[1
]}

Raduwan, Hamidah ^{[1
]}

Chen, Tse-Yu ^{[1
]}

Arora, Gunjan ^{[1
]}

Halene, Stephanie ^{[6
]}

Shaw, Albert C. ^{[1
]}

Palm, Noah W. ^{[2
]}

Flavell, Richard A. ^{[2
]}

Parkos, Charles A. ^{[4
]}

Thangamani, Saravanan ^{[3
]}

Ring, Aaron M. ^{[2
,9
]}

Fikrig, Erol ^{[1
]}

机构：

[1] Yale Univ, Sch Med, Dept Internal Med, Sect Infect Dis, New Haven, CT 06510 USA

[2] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA

[3] State Univ New York, Upstate Med Univ, Dept Microbiol & Immunol, Syracuse, NY USA

[4] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA

[5] Yale Sch Med, Bioinformat Support Program, Cushing Whitney Med Lib, New Haven, CT USA

[6] Yale Univ, Sch Med, Dept Internal Med, Sect Hematol, New Haven, CT USA

[7] Univ Complutense Madrid, Fac Farm, Dept Fisiol, Madrid 28040, Spain

[8] Arcus Biosci, Hayward, CA USA

[9] Fred Hutchinson Canc Ctr, Translat Sci & Therapeut Div, Seattle, WA USA

来源：

SCIENCE IMMUNOLOGY | 2024年 / 9卷 / 98期

基金：

美国国家卫生研究院;

关键词：

INTEGRIN-ASSOCIATED PROTEIN; ZIKA VIRUS-INFECTION; SIRP-ALPHA; NEUTROPHIL MIGRATION; MOSQUITO; BINDING; ADHESION; LIGAND; MEMBER; CELLS;

D O I：

10.1126/sciimmunol.adk9872

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 Aedes aegypti mosquito is a vector of many infectious agents, including flaviviruses such as Zika virus. Components of mosquito saliva have pleomorphic effects on the vertebrate host to enhance blood feeding, and these changes also create a favorable niche for pathogen replication and dissemination. Here, we demonstrate that human CD47, which is known to be involved in various immune processes, interacts with a 34-kilodalton mosquito salivary protein named Nest1. Nest1 is up-regulated in blood-fed female A. aegypti and facilitates Zika virus dissemination in human skin explants. Nest1 has a stronger affinity for CD47 than its natural ligand, signal regulatory protein alpha, competing for binding at the same interface. The interaction between Nest1 with CD47 suppresses phagocytosis by human macrophages and inhibits proinflammatory responses by white blood cells, thereby suppressing antiviral responses in the skin. This interaction elucidates how an arthropod protein alters the human response to promote arbovirus infectivity.

引用

页数：15