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 KoenenMusa M. Mhlanga, Dimitri A. Diavatopoulos, Triantafyllos Chavakis, Mihai G. Netea

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Article number108387
JournalCell Reports
Issue number7
Early online date17 Nov 2020
Publication statusPublished - 17 Nov 2020

Keywords / Materials (for Non-textual outputs)

  • innate immune memory
  • trained immunity
  • neutrophil
  • polymorphonuclear leukocytes
  • BCG
  • nonspecific effects of vaccines
  • epigenetics


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