Immunological Fingerprints of Controllers Developing Neutralizing HIV-1 Antibodies
Name
1-s2.0-S2211124719317528-main.pdf
Description
Published version
Size
4.57 MB
Format
Adobe PDF
Checksum (MD5)
4bd8a9d6e71d9f730e1ec9f9dd91900e
Author(s)
Martin-Gayo, Enrique
Gao, Ce
Chen, Hsiao Rong
Ouyang, Zhengyu
Kim, Dhohyung
Kolb, Kellie Elizabeth
Shalek, Alexander K
Walker, Bruce D.
Lichterfeld, Mathias
Yu, Xu G.
Date Issued
January 2020
Journal
Cell Reports
Publisher
Elsevier BV
Citation
Martin-Gayo, Enrique et al. "Immunological Fingerprints of Controllers Developing Neutralizing HIV-1 Antibodies." Cell Reports 30, 4 (January 2020): P984-996.e4 © 2019 The Author(s)
Version
Final published version
Abstract
The induction of broadly neutralizing antibodies (bnAbs) is highly desired for an effective vaccine against HIV-1. Typically, bnAbs develop in patients with high viremia, but they can also evolve in some untreated HIV-1 controllers with low viral loads. Here, we identify a subgroup of neutralizer-controllers characterized by myeloid DCs (mDCs) with a distinct inflammatory signature and a superior ability to prime T follicular helper (Tfh)-like cells in an STAT4-dependent fashion. This distinct immune profile is associated with a higher frequency of Tfh-like cells in peripheral blood (pTfh) and an enrichment for Tfh-defining genes in circulating CD4+ T cells. Correspondingly, monocytes from this neutralizer controller subgroup upregulate genes encoding for chemotaxis and inflammation, and they secrete high levels of IL-12 in response to TLR stimulation. Our results suggest the existence of multi-compartment immune networks between mDCs, Tfh, and monocytes that may facilitate the development of bnAbs in a subgroup of HIV-1 controllers.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.celrep.2019.12.087
