An Integrin/MFG-E8 shuttle loads HIV-1 viral like particles onto follicular dendritic cells in mouse lymph node

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Abstract

During human immunodeficiency virus-1 (HIV-1) infection lymphoid organ follicular dendritic cells (FDCs) serve as a reservoir for infectious virus and an obstacle to curative therapies. Here, we identify a subset of lymphoid organ sinus lining macrophage (SMs) that provide a cell-cell contact portal, which facilitates the uptake of HIV-1 viral like particles (VLPs) by FDCs and B cells in mouse lymph node. Central for portal function is the bridging glycoprotein MFG-E8. Using a phosphatidylserine binding domain and an RGD motif, MFG-E8 helps target HIV-1 VLPs to av integrin bearing SMs. Lack of MFG-E8 or integrin blockade severely limits HIV-1 VLP spread onto FDC networks. Direct SM-FDC virion transfer also depends upon short-lived FDC network abutment, likely triggered by SCSM antigen uptake. This provides a mechanism for rapid FDC loading broadening the opportunity for rare, antigen reactive follicular B cells to acquire antigen, and a means for HIV virions to accumulate on the FDC network.

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All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

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Chung Park

B-cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, Bethesda, United States

Competing interests
The authors declare that no competing interests exist.
John H Kehrl

B-cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, Bethesda, United States

For correspondence
jkehrl@niaid.nih.gov

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-6526-159X

Funding

No external funding was received for this work.

Ethics

Animal experimentation: The NIAID Animal Care and Use Committee (ACUC) at the National Institutes of Health approved all the animal experiments and protocols used in the study, under protocol LIR-15E.

Human subjects: Human peripheral blood mononuclear cells (PBMCs) were collected from healthy donors through a NIH Department of Transfusion Medicine protocol that was approved by the Institutional Review Board of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health.

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.