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Translocated microbiome composition determines immunological outcome in treated HIV infection.
Nganou-Makamdop, Krystelle; Talla, Aarthi; Sharma, Ashish Arunkumar; Darko, Sam; Ransier, Amy; Laboune, Farida; Chipman, Jeffrey G; Beilman, Gregory J; Hoskuldsson, Torfi; Fourati, Slim; Schmidt, Thomas E; Arumugam, Sahaana; Lima, Noemia S; Moon, Damee; Callisto, Samuel; Schoephoerster, Jordan; Tomalka, Jeffery; Mugyenyi, Peter; Ssali, Francis; Muloma, Proscovia; Ssengendo, Patrick; Leda, Ana R; Cheu, Ryan K; Flynn, Jacob K; Morou, Antigoni; Brunet-Ratnasingham, Elsa; Rodriguez, Benigno; Lederman, Michael M; Kaufmann, Daniel E; Klatt, Nichole R; Kityo, Cissy; Brenchley, Jason M; Schacker, Timothy W; Sekaly, Rafick P; Douek, Daniel C.
Afiliação
  • Nganou-Makamdop K; Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Institute of Clinical and Molecular Virology, University Hospital Erlangen, 91054 Erlangen, Germany.
  • Talla A; Department of Pathology, Case Western Reserve University, Cleveland, OH 10900, USA; Allen Institute for Immunology, Seattle, WA 98109, USA.
  • Sharma AA; Department of Pathology, Case Western Reserve University, Cleveland, OH 10900, USA; Pathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Darko S; Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Ransier A; Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Laboune F; Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Chipman JG; Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
  • Beilman GJ; Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
  • Hoskuldsson T; Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
  • Fourati S; Department of Pathology, Case Western Reserve University, Cleveland, OH 10900, USA; Pathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Schmidt TE; Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
  • Arumugam S; Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Lima NS; Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Moon D; Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Callisto S; Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
  • Schoephoerster J; Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
  • Tomalka J; Department of Pathology, Case Western Reserve University, Cleveland, OH 10900, USA; Pathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Mugyenyi P; Joint Clinical Research Center, Kampala, Uganda.
  • Ssali F; Joint Clinical Research Center, Kampala, Uganda.
  • Muloma P; Joint Clinical Research Center, Kampala, Uganda.
  • Ssengendo P; Joint Clinical Research Center, Kampala, Uganda.
  • Leda AR; Department of Pediatrics, Miller School of Medicine, University of Miami, Miami, FL 33124, USA.
  • Cheu RK; Department of Pediatrics, Miller School of Medicine, University of Miami, Miami, FL 33124, USA.
  • Flynn JK; Barrier Immunity Section, Laboratory of Viral Diseases, NIAID/NIH, Bethesda, MD 20892, USA.
  • Morou A; Research Centre of the Centre Hospitalier de l'Université de Montréal, Montreal, QC H3C 3J7, Canada; Université de Montréal, Montreal, QC H3C 3J7, Canada; Roche Diagnostics GmbH, 82377 Penzberg, Germany.
  • Brunet-Ratnasingham E; Research Centre of the Centre Hospitalier de l'Université de Montréal, Montreal, QC H3C 3J7, Canada; Université de Montréal, Montreal, QC H3C 3J7, Canada.
  • Rodriguez B; Case Western Reserve University School of Medicine, Cleveland, OH 10900, USA.
  • Lederman MM; Case Western Reserve University School of Medicine, Cleveland, OH 10900, USA.
  • Kaufmann DE; Research Centre of the Centre Hospitalier de l'Université de Montréal, Montreal, QC H3C 3J7, Canada; Université de Montréal, Montreal, QC H3C 3J7, Canada.
  • Klatt NR; Department of Pediatrics, Miller School of Medicine, University of Miami, Miami, FL 33124, USA.
  • Kityo C; Joint Clinical Research Center, Kampala, Uganda.
  • Brenchley JM; Barrier Immunity Section, Laboratory of Viral Diseases, NIAID/NIH, Bethesda, MD 20892, USA.
  • Schacker TW; Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: schacker@umn.edu.
  • Sekaly RP; Department of Pathology, Case Western Reserve University, Cleveland, OH 10900, USA; Pathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA. Electronic address: rafick.sekaly@emory.edu.
  • Douek DC; Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: ddouek@mail.nih.gov.
Cell ; 184(15): 3899-3914.e16, 2021 07 22.
Article em En | MEDLINE | ID: mdl-34237254
ABSTRACT
The impact of the microbiome on HIV disease is widely acknowledged although the mechanisms downstream of fluctuations in microbial composition remain speculative. We detected rapid, dynamic changes in translocated microbial constituents during two years after cART initiation. An unbiased systems biology approach revealed two distinct pathways driven by changes in the abundance ratio of Serratia to other bacterial genera. Increased CD4 T cell numbers over the first year were associated with high Serratia abundance, pro-inflammatory innate cytokines, and metabolites that drive Th17 gene expression signatures and restoration of mucosal integrity. Subsequently, decreased Serratia abundance and downregulation of innate cytokines allowed re-establishment of systemic T cell homeostasis promoting restoration of Th1 and Th2 gene expression signatures. Analyses of three other geographically distinct cohorts of treated HIV infection established a more generalized principle that changes in diversity and composition of translocated microbial species influence systemic inflammation and consequently CD4 T cell recovery.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por HIV / Microbioma Gastrointestinal Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Limite: Humans País como assunto: Africa Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por HIV / Microbioma Gastrointestinal Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Limite: Humans País como assunto: Africa Idioma: En Ano de publicação: 2021 Tipo de documento: Article