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Martin-Gayo, Enrique; Gao, Ce; Chen, Hsiao Rong; Ouyang, Zhengyu; Kim, Dhohyung; Kolb, Kellie E.; Shalek, Alex K.; Walker, Bruce D.; Lichterfeld, Mathias; Yu, Xu G.
Cell reports, 01/2020, Letnik: 30, Številka: 4Journal Article
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. Display omitted •HIV-1 controllers with neutralizing Abs are subdivided in two subgroups (Nt1 and Nt2)•HIV-1-specific antibodies from Nt2 individuals display superior neutralization potency•Nt2 exhibit distinct transcriptional signatures in DC, monocytes, and CD4 T cells•Transcriptional and functional data suggest improved DC-pTFH interactions in Nt2 Martin-Gayo et al. identify a subgroup of HIV-1 controllers who mount potent neutralizing antibodies against the virus. The distinguishing features of this subset of individuals include a tightly regulated network of transcriptional and functional interactions between dendritic cells, T cells, and monocytes.
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in: SICRIS
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