The human CD47 checkpoint is targeted by an immunosuppressive <i>Aedes aegypti</i> salivary factor to enhance arboviral skin infectivity
The <i>Aedes aegypti</i> 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 <i>A. aegypti</i> and facilitates Zika virus dissemination in human skin explants. Nest1 has a stronger affinity for CD47 than its natural ligand, signal regulatory protein α, 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.
Authors
- Allen T. Esterly (ORCID: https://orcid.org/0000-0003-1132-6797)
- Gemma Vidal‐Pedrola
- Rolando García-Milian (ORCID: https://orcid.org/0000-0003-1557-566X)
- Esen Sefik (ORCID: https://orcid.org/0000-0002-6807-3498)
- Connor Rosen (ORCID: https://orcid.org/0000-0003-2442-3676)
- John D. Huck
- Albert C. Shaw (ORCID: https://orcid.org/0000-0003-4970-7640)
- Noah W. Palm (ORCID: https://orcid.org/0000-0001-7262-9455)
- Erol Fikrig (ORCID: https://orcid.org/0000-0002-5884-6047)
- Hamidah Raduwan (ORCID: https://orcid.org/0000-0002-4939-7809)
- Verónica Azcutia (ORCID: https://orcid.org/0000-0003-2160-5175)
- Alejandro Marín-López (ORCID: https://orcid.org/0000-0003-2840-1722)
- Stephanie Halene (ORCID: https://orcid.org/0000-0002-2737-9810)
- Aaron M. Ring (ORCID: https://orcid.org/0000-0003-3699-2446)
- Richard A. Flavell (ORCID: https://orcid.org/0000-0003-4461-0778)
- Tse-Yu Chen (ORCID: https://orcid.org/0000-0002-8281-909X)
- Gunjan Arora (ORCID: https://orcid.org/0000-0003-0575-6205)
- Charles A. Parkos (ORCID: https://orcid.org/0000-0002-2490-7657)
- Saravanan Thangamani (ORCID: https://orcid.org/0000-0002-4269-5993)
Institutions
- SUNY Upstate Medical University (US)
- University of Michigan (US)
- Whitney Museum of American Art (US)
- Yale University (US)
Publication Details
- Journal
- Science Immunology
- Published
- 2024-08-09
- DOI
- https://doi.org/10.1126/sciimmunol.adk9872
- Citations
- 5
- Primary Topic
- Mosquito-borne diseases and control
- Type
- article
- Field-Weighted Citation Impact
- 2.71
Funders
- Yale University
- State University of New York
- National Institutes of Health