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Cell Rep DOI:10.1016/j.celrep.2019.12.087

Immunological Fingerprints of Controllers Developing Neutralizing HIV-1 Antibodies.

Publication TypeJournal Article
Year of Publication2020
AuthorsMartin-Gayo, E, Gao, C, Chen, HRong, Ouyang, Z, Kim, D, Kolb, KE, Shalek, AK, Walker, BD, Lichterfeld, M, Yu, XG
JournalCell Rep
Volume30
Issue4
Pages984-996.e4
Date Published2020 Jan 28
ISSN2211-1247
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.

DOI10.1016/j.celrep.2019.12.087
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/31995767?dopt=Abstract

Alternate JournalCell Rep
PubMed ID31995767