Immunological Fingerprints of Controllers Developing Neutralizing HIV-1 Antibodies

• Main Authors: Martin-Gayo, Enrique (Author), Gao, Ce (Author), Chen, Hsiao Rong (Author), Ouyang, Zhengyu (Author), Kim, Dhohyung (Author), Kolb, Kellie Elizabeth (Author), Shalek, Alexander K (Author), Walker, Bruce D. (Author), Lichterfeld, Mathias (Author), Yu, Xu G. (Author)
• Other Authors: Massachusetts Institute of Technology. Department of Chemistry (Contributor), Massachusetts Institute of Technology. Institute for Medical Engineering & Science (Contributor), Koch Institute for Integrative Cancer Research at MIT (Contributor)
• Format: Article
• Language: English
• Published: Elsevier BV, 2020-09-21T19:42:24Z.
• Subjects: Article
• Online Access: Get fulltext

 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.