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.
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 language | English |
---|---|
Article number | 108387 |
Journal | Cell Reports |
Volume | 33 |
Issue number | 7 |
Early online date | 17 Nov 2020 |
DOIs | |
Publication status | Published - 17 Nov 2020 |
Keywords
- innate immune memory
- trained immunity
- neutrophil
- polymorphonuclear leukocytes
- BCG
- nonspecific effects of vaccines
- epigenetics
Fingerprint
Dive into the research topics of 'BCG Vaccination Induces Long-Term Functional Reprogramming of Human Neutrophils'. Together they form a unique fingerprint.Profiles
-
Triantafyllos Chavakis
- Deanery of Clinical Sciences - Visiting Professor
- Centre for Cardiovascular Science
Person: Academic: Research Active