[PDF][PDF] Immunological fingerprints of controllers developing neutralizing HIV-1 antibodies

E Martin-Gayo, C Gao, HR Chen, Z Ouyang, D Kim… - Cell reports, 2020 - cell.com
E Martin-Gayo, C Gao, HR Chen, Z Ouyang, D Kim, KE Kolb, AK Shalek, BD Walker
Cell reports, 2020cell.com
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 …
Summary
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.
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