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Immunological Fingerprints of Controllers Developing Neutralizing HIV-1 Antibodies.
Martin-Gayo, Enrique; Gao, Ce; Chen, Hsiao Rong; Ouyang, Zhengyu; Kim, Dhohyung; Kolb, Kellie E; Shalek, Alex K; Walker, Bruce D; Lichterfeld, Mathias; Yu, Xu G.
Afiliação
  • Martin-Gayo E; Ragon Institute of MGH, MIT, and Harvard, Boston, MA, USA; Universidad Autónoma de Madrid, Hospital de la Princesa, Madrid, Spain. Electronic address: enrique.martin@uam.es.
  • Gao C; Ragon Institute of MGH, MIT, and Harvard, Boston, MA, USA.
  • Chen HR; Ragon Institute of MGH, MIT, and Harvard, Boston, MA, USA.
  • Ouyang Z; Ragon Institute of MGH, MIT, and Harvard, Boston, MA, USA.
  • Kim D; Ragon Institute of MGH, MIT, and Harvard, Boston, MA, USA.
  • Kolb KE; 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.
  • Shalek AK; 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.
  • Walker BD; 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.
  • Lichterfeld M; 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.
  • Yu XG; 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. Electronic address: xyu@mgh.har
Cell Rep ; 30(4): 984-996.e4, 2020 01 28.
Article em En | MEDLINE | ID: mdl-31995767
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.
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 1_ASSA2030 / 2_ODS3 Base de dados: MEDLINE Assunto principal: Células Dendríticas / Monócitos / Anticorpos Anti-HIV / Linfócitos T CD4-Positivos / Infecções por HIV / HIV-1 / Linfócitos T Auxiliares-Indutores / Anticorpos Neutralizantes Tipo de estudo: Prognostic_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Cell Rep Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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Buscar no Google

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 1_ASSA2030 / 2_ODS3 Base de dados: MEDLINE Assunto principal: Células Dendríticas / Monócitos / Anticorpos Anti-HIV / Linfócitos T CD4-Positivos / Infecções por HIV / HIV-1 / Linfócitos T Auxiliares-Indutores / Anticorpos Neutralizantes Tipo de estudo: Prognostic_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Cell Rep Ano de publicação: 2020 Tipo de documento: Article