Immunological Fingerprints of Controllers Developing Neutralizing HIV-1 Antibodies
Enrique Martin-Gayo,
Ce Gao,
Hsiao Rong Chen,
Zhengyu Ouyang,
Dhohyung Kim,
Kellie E. Kolb,
Alex K. Shalek,
Bruce D. Walker,
Mathias Lichterfeld,
Xu G. Yu
Affiliations
Enrique Martin-Gayo
Ragon Institute of MGH, MIT, and Harvard, Boston, MA, USA; Universidad Autónoma de Madrid, Hospital de la Princesa, Madrid, Spain; Corresponding author
Ce Gao
Ragon Institute of MGH, MIT, and Harvard, Boston, MA, USA
Hsiao Rong Chen
Ragon Institute of MGH, MIT, and Harvard, Boston, MA, USA
Zhengyu Ouyang
Ragon Institute of MGH, MIT, and Harvard, Boston, MA, USA
Dhohyung Kim
Ragon Institute of MGH, MIT, and Harvard, Boston, MA, USA
Kellie E. Kolb
Ragon Institute of MGH, MIT, and Harvard, Boston, MA, USA; Department of Chemistry, MIT Institute for Medical Engineering and Science (IMES), MIT, Cambridge, MA, USA; Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
Alex K. Shalek
Ragon Institute of MGH, MIT, and Harvard, Boston, MA, USA; Department of Chemistry, MIT Institute for Medical Engineering and Science (IMES), MIT, Cambridge, MA, USA; Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
Bruce D. Walker
Ragon Institute of MGH, MIT, and Harvard, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA
Mathias Lichterfeld
Ragon Institute of MGH, MIT, and Harvard, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Infectious Disease Division, Brigham and Women’s Hospital, Boston, MA, USA; Infectious Disease Division, Massachusetts General Hospital, Boston, MA, USA
Xu G. Yu
Ragon Institute of MGH, MIT, and Harvard, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Infectious Disease Division, Brigham and Women’s Hospital, Boston, MA, USA; Infectious Disease Division, Massachusetts General Hospital, Boston, MA, USA; Corresponding author
Summary: 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. : 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. Keywords: HIV, dendritic cell, systems biology, CD4 T cell, bnAb, controller, neutralizer, monocyte, B cell, RNAseq
