BCG Vaccination Induces Long-Term Functional Reprogramming of Human Neutrophils

• Published in: Cell reports (Cambridge) Vol. 33; no. 7; p. 108387
• Main Authors: Moorlag, Simone J.C.F.M., Rodriguez-Rosales, Yessica Alina, Gillard, Joshua, Fanucchi, Stephanie, Theunissen, Kate, Novakovic, Boris, de Bont, Cynthia M., Negishi, Yutaka, Fok, Ezio T., Kalafati, Lydia, Verginis, Panayotis, Mourits, Vera P., Koeken, Valerie A.C.M., de Bree, L. Charlotte J., Pruijn, Ger J.M., Fenwick, Craig, van Crevel, Reinout, Joosten, Leo A.B., Joosten, Irma, Koenen, Hans, Mhlanga, Musa M., Diavatopoulos, Dimitri A., Chavakis, Triantafyllos, Netea, Mihai G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.11.2020; Cell Press; Elsevier
• Subjects: BCG; epigenetics; innate immune memory; neutrophil; nonspecific effects of vaccines; polymorphonuclear leukocytes; trained immunity; polymorphonuclear leukocytes; innate immune memory; BCG; trained immunity; neutrophil; epigenetics; nonspecific effects of vaccines
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.108387

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. [Display omitted] •BCG vaccination of humans induces long-term immunophenotypic changes in neutrophils•BCG increases antimicrobial activity of neutrophils against unrelated pathogens•BCG-induced functional changes associate with modifications in histone methylation•Trained immunity may be a therapeutic target in neutrophil-mediated diseases Moorlag et al. show that BCG vaccination induces long-lasting functional changes in human neutrophils, characterized by increased expression of activation markers and enhanced antimicrobial function upon secondary stimulation. These findings highlight the potential of trained immunity as a therapeutic target to modulate neutrophil effector function.