Cell Reports (Nov 2020)
BCG Vaccination Induces Long-Term Functional Reprogramming of Human Neutrophils
- Simone J.C.F.M. Moorlag,
- Yessica Alina Rodriguez-Rosales,
- Joshua Gillard,
- Stephanie Fanucchi,
- Kate Theunissen,
- Boris Novakovic,
- Cynthia M. de Bont,
- Yutaka Negishi,
- Ezio T. Fok,
- Lydia Kalafati,
- Panayotis Verginis,
- Vera P. Mourits,
- Valerie A.C.M. Koeken,
- L. Charlotte J. de Bree,
- Ger J.M. Pruijn,
- Craig Fenwick,
- Reinout van Crevel,
- Leo A.B. Joosten,
- Irma Joosten,
- Hans Koenen,
- Musa M. Mhlanga,
- Dimitri A. Diavatopoulos,
- Triantafyllos Chavakis,
- Mihai G. Netea
Affiliations
- Simone J.C.F.M. Moorlag
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
- Yessica Alina Rodriguez-Rosales
- Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center, Nijmegen, the Netherlands
- Joshua Gillard
- Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboudumc, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases, Radboudumc, Nijmegen, the Netherlands
- Stephanie Fanucchi
- Division of Chemical, Systems & Synthetic Biology, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, Institute of Infectious Disease & Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Kate Theunissen
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
- Boris Novakovic
- Epigenetics, Murdoch Children’s Research Institute, Royal Children’s Hospital, and Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia
- Cynthia M. de Bont
- Department of Biomolecular Chemistry, Institute for Molecules and Materials (IMM), Radboud University, Nijmegen, the Netherlands
- Yutaka Negishi
- Epigenomics & Single Cell Biophysics Group, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University, Nijmegen, the Netherlands; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands
- Ezio T. Fok
- Epigenomics & Single Cell Biophysics Group, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University, Nijmegen, the Netherlands; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands
- Lydia Kalafati
- Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; Laboratory of Immune Regulation and Tolerance, Autoimmunity and Inflammation, Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece
- Panayotis Verginis
- Laboratory of Immune Regulation and Tolerance, Autoimmunity and Inflammation, Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece
- Vera P. Mourits
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
- Valerie A.C.M. Koeken
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM) & TWINCORE, joint ventures between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany
- L. Charlotte J. de Bree
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands; Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark; Odense Patient Data Explorative Network, University of Southern Denmark/Odense University Hospital, Odense, Denmark
- Ger J.M. Pruijn
- Department of Biomolecular Chemistry, Institute for Molecules and Materials (IMM), Radboud University, Nijmegen, the Netherlands
- Craig Fenwick
- Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
- Reinout van Crevel
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
- Leo A.B. Joosten
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
- Irma Joosten
- Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center, Nijmegen, the Netherlands
- Hans Koenen
- Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center, Nijmegen, the Netherlands
- Musa M. Mhlanga
- Epigenomics & Single Cell Biophysics Group, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University, Nijmegen, the Netherlands; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands
- Dimitri A. Diavatopoulos
- Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboudumc, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases, Radboudumc, Nijmegen, the Netherlands
- Triantafyllos Chavakis
- Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany
- Mihai G. Netea
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands; Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany; Corresponding author
- Journal volume & issue
-
Vol. 33,
no. 7
p. 108387
Abstract
Summary: The tuberculosis vaccine bacillus Calmette-Guérin (BCG) protects against some heterologous infections, probably via induction of non-specific innate immune memory in monocytes and natural killer (NK) cells, a process known as trained immunity. Recent studies have revealed that the induction of trained immunity is associated with a bias toward granulopoiesis in bone marrow hematopoietic progenitor cells, but it is unknown whether BCG vaccination also leads to functional reprogramming of mature neutrophils. Here, we show that BCG vaccination of healthy humans induces long-lasting changes in neutrophil phenotype, characterized by increased expression of activation markers and antimicrobial function. The enhanced function of human neutrophils persists for at least 3 months after vaccination and is associated with genome-wide epigenetic modifications in trimethylation at histone 3 lysine 4. Functional reprogramming of neutrophils by the induction of trained immunity might offer novel therapeutic strategies in clinical conditions that could benefit from modulation of neutrophil effector function.
