BCG Vaccination Induces Long-Term Functional Reprogramming of Human Neutrophils.
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.
['Moorlag|Simone J C F M|SJCFM|', 'Rodriguez-Rosales|Yessica Alina|YA|', 'Gillard|Joshua|J|', 'Fanucchi|Stephanie|S|', 'Theunissen|Kate|K|', 'Novakovic|Boris|B|', 'de Bont|Cynthia M|CM|', 'Negishi|Yutaka|Y|', 'Fok|Ezio T|ET|', 'Kalafati|Lydia|L|', 'Verginis|Panayotis|P|', 'Mourits|Vera P|VP|', 'Koeken|Valerie A C M|VACM|', 'de Bree|L Charlotte J|LCJ|', 'Pruijn|Ger J M|GJM|', 'Fenwick|Craig|C|', 'van Crevel|Reinout|R|', 'Joosten|Leo A B|LAB|', 'Joosten|Irma|I|', 'Koenen|Hans|H|', 'Mhlanga|Musa M|MM|', 'Diavatopoulos|Dimitri A|DA|', 'Chavakis|Triantafyllos|T|', 'Netea|Mihai G|MG|']
D056704:Adaptive Immunity D000328:Adult D000368:Aged D001500:BCG Vaccine D065150:Cellular Reprogramming D005260:Female D006801:Humans D007113:Immunity, Innate D007694:Killer Cells, Natural D008297:Male D008875:Middle Aged D009000:Monocytes D009169:Mycobacterium tuberculosis D009504:Neutrophils D014376:Tuberculosis D014611:Vaccination
BCG neutrophil innate immune memory trained immunity epigenetics nonspecific effects of vaccines polymorphonuclear leukocytes