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

Cell Reports (Jan 2020)

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

Journal volume & issue: Vol. 30, no. 4
pp. 984 – 996.e4

Abstract

Read online

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

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

About the journal