Immunological Fingerprints of Controllers Developing Neutralizing HIV-1 Antibodies

  • Biology
  • Genomics
  • Immunology
  • Infectious Disease
  • Medicine
  • Kellie Kolb
  • Alex K. Shalek
  • Martin-Gayo et al.▾
    Martin-Gayo, E., Gao, C., Chen, H.R., Ouyang, Z., Kim, D., Kolb, K.E., Shalek, A.K., Walker, B.D., Lichterfeld, M., Yu, X.G.
  • Cell Reports , Volume 30
  • January, 2020
Biology
Genomics
Immunology
Infectious Disease
Medicine
Kellie Kolb
Alex K. Shalek

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.

Immunological Fingerprints of Controllers Developing Neutralizing HIV-1 Antibodies