Immunological Fingerprints of Controllers Developing Neutralizing HIV-1 Antibodies
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.; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Department of Chemistry; Massachusetts Institute of Technology. Institute for Medical Engineering & Science; Koch Institute for Integrative Cancer Research at MIT
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)
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