Immunological Fingerprints of Controllers Developing Neutralizing HIV-1 Antibodies

Biology Biology
Genomics Genomics
Immunology Immunology
Infectious Disease Infectious Disease
Medicine Medicine
Alex K. Shalek Alex K. Shalek
Kellie Kolb Kellie Kolb

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


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.