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A Molecular Signature in Blood Reveals a Role for p53 in Regulating Malaria-Induced Inflammation.
Tran, Tuan M; Guha, Rajan; Portugal, Silvia; Skinner, Jeff; Ongoiba, Aissata; Bhardwaj, Jyoti; Jones, Marcus; Moebius, Jacqueline; Venepally, Pratap; Doumbo, Safiatou; DeRiso, Elizabeth A; Li, Shanping; Vijayan, Kamalakannan; Anzick, Sarah L; Hart, Geoffrey T; O'Connell, Elise M; Doumbo, Ogobara K; Kaushansky, Alexis; Alter, Galit; Felgner, Phillip L; Lorenzi, Hernan; Kayentao, Kassoum; Traore, Boubacar; Kirkness, Ewen F; Crompton, Peter D.
Afiliação
  • Tran TM; Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA; Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Ryan White
  • Guha R; Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA.
  • Portugal S; Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA; Center for Infectious Diseases-Parasitology, Heidelberg University Hospital, Heidelberg 69120, Germany.
  • Skinner J; Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA.
  • Ongoiba A; Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, BP 1805, Point G, Bamako, Mali.
  • Bhardwaj J; Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Ryan White Center for Pediatric Infectious Disease and Global Health, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • Jones M; Genomic Medicine Group, J. Craig Venter Institute, Rockville, MD 20850, USA.
  • Moebius J; Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA.
  • Venepally P; Genomic Medicine Group, J. Craig Venter Institute, Rockville, MD 20850, USA.
  • Doumbo S; Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, BP 1805, Point G, Bamako, Mali.
  • DeRiso EA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA.
  • Li S; Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA.
  • Vijayan K; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA.
  • Anzick SL; Rocky Mountain Laboratories, Genomics Unit, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840, USA.
  • Hart GT; Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA; Division of Infectious Disease and International Medicine, Department of Medicine, Center for Immunology, University of Minnesota, Minne
  • O'Connell EM; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Doumbo OK; Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, BP 1805, Point G, Bamako, Mali.
  • Kaushansky A; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA.
  • Alter G; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA.
  • Felgner PL; Division of Infectious Diseases, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
  • Lorenzi H; Department of Infectious Diseases, J. Craig Venter Institute, Rockville, MD 20850, USA.
  • Kayentao K; Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, BP 1805, Point G, Bamako, Mali.
  • Traore B; Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, BP 1805, Point G, Bamako, Mali.
  • Kirkness EF; Genomic Medicine Group, J. Craig Venter Institute, Rockville, MD 20850, USA.
  • Crompton PD; Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA. Electronic address: pcrompton@niaid.nih.gov.
Immunity ; 51(4): 750-765.e10, 2019 10 15.
Article em En | MEDLINE | ID: mdl-31492649
Immunity that controls parasitemia and inflammation during Plasmodium falciparum (Pf) malaria can be acquired with repeated infections. A limited understanding of this complex immune response impedes the development of vaccines and adjunctive therapies. We conducted a prospective systems biology study of children who differed in their ability to control parasitemia and fever following Pf infection. By integrating whole-blood transcriptomics, flow-cytometric analysis, and plasma cytokine and antibody profiles, we demonstrate that a pre-infection signature of B cell enrichment, upregulation of T helper type 1 (Th1) and Th2 cell-associated pathways, including interferon responses, and p53 activation associated with control of malarial fever and coordinated with Pf-specific immunoglobulin G (IgG) and Fc receptor activation to control parasitemia. Our hypothesis-generating approach identified host molecules that may contribute to differential clinical outcomes during Pf infection. As a proof of concept, we have shown that enhanced p53 expression in monocytes attenuated Plasmodium-induced inflammation and predicted protection from fever.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Plasmodium falciparum / Proteínas Sanguíneas / Linfócitos B / Proteína Supressora de Tumor p53 / Malária Falciparum / Células Th2 / Células Th1 / Inflamação Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Animals / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Immunity Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Plasmodium falciparum / Proteínas Sanguíneas / Linfócitos B / Proteína Supressora de Tumor p53 / Malária Falciparum / Células Th2 / Células Th1 / Inflamação Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Animals / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Immunity Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2019 Tipo de documento: Article