BCG Vaccination Induces Long-Term Functional Reprogramming of Human Neutrophils

TLDR

BCG vaccination protects against heterologous infections by inducing trained immunity in monocytes and NK cells. This study examined whether BCG vaccination also induces functional reprogramming of mature neutrophils. BCG vaccination produced long‑lasting neutrophil reprogramming, evidenced by increased activation markers, enhanced antimicrobial activity persisting for at least three months, and genome‑wide H3K4 trimethylation changes, suggesting potential therapeutic applications.

Abstract

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.