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 Koenen; Musa M. Mhlanga; Dimitri A. Diavatopoulos; Triantafyllos Chavakis; Mihai G. Netea

doi:10.1016/j.celrep.2020.108387

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 journal › Article › peer-review

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.

Original language	English
Article number	108387
Journal	Cell Reports
Volume	33
Issue number	7
Early online date	17 Nov 2020
DOIs	https://doi.org/10.1016/j.celrep.2020.108387
Publication status	Published - 17 Nov 2020

Keywords

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

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10.1016/j.celrep.2020.108387

1-s2.0-S2211124720313760-mainFinal published version, 3.45 MBLicence: CC BY-NC-ND

https://linkinghub.elsevier.com/retrieve/pii/S2211124720313760

Triantafyllos Chavakis
- Deanery of Clinical Sciences - Visiting Professor
- Centre for Cardiovascular Science
Person: Academic: Research Active

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Moorlag, S. J. C. F. M., Rodriguez-Rosales, Y. A., Gillard, J., Fanucchi, S., Theunissen, K., Novakovic, B., De Bont, C. M., Negishi, Y., Fok, E. T., Kalafati, L., Verginis, P., Mourits, V. P., Koeken, V. A. C. M., De Bree, L. C. J., Pruijn, G. J. M., Fenwick, C., Van Crevel, R., Joosten, L. A. B., Joosten, I., ... Netea, M. G. (2020). BCG Vaccination Induces Long-Term Functional Reprogramming of Human Neutrophils. Cell Reports, 33(7), [108387]. https://doi.org/10.1016/j.celrep.2020.108387

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title = "BCG Vaccination Induces Long-Term Functional Reprogramming of Human Neutrophils",

abstract = "SummaryThe tuberculosis vaccine bacillus Calmette-Gu{\'e}rin (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.",

keywords = "innate immune memory, trained immunity, neutrophil, polymorphonuclear leukocytes, BCG, nonspecific effects of vaccines, epigenetics",

author = "Moorlag, {Simone J.C.F.M.} and Rodriguez-Rosales, {Yessica Alina} and Joshua Gillard and Stephanie Fanucchi and Kate Theunissen and Boris Novakovic and {De Bont}, {Cynthia M.} and Yutaka Negishi and Fok, {Ezio T.} and Lydia Kalafati and Panayotis Verginis and Mourits, {Vera P.} and Koeken, {Valerie A.C.M.} and {De Bree}, {L. Charlotte J.} and Pruijn, {Ger J.M.} and Craig Fenwick and {Van Crevel}, Reinout and Joosten, {Leo A.B.} and Irma Joosten and Hans Koenen and Mhlanga, {Musa M.} and Diavatopoulos, {Dimitri A.} and Triantafyllos Chavakis and Netea, {Mihai G.}",

year = "2020",

month = nov,

day = "17",

doi = "10.1016/j.celrep.2020.108387",

language = "English",

volume = "33",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "7",

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Moorlag, SJCFM, Rodriguez-Rosales, YA, Gillard, J, Fanucchi, S, Theunissen, K, Novakovic, B, De Bont, CM, Negishi, Y, Fok, ET, Kalafati, L, Verginis, P, Mourits, VP, Koeken, VACM, De Bree, LCJ, Pruijn, GJM, Fenwick, C, Van Crevel, R, Joosten, LAB, Joosten, I, Koenen, H, Mhlanga, MM, Diavatopoulos, DA, Chavakis, T & Netea, MG 2020, 'BCG Vaccination Induces Long-Term Functional Reprogramming of Human Neutrophils', Cell Reports, vol. 33, no. 7, 108387. https://doi.org/10.1016/j.celrep.2020.108387

TY - JOUR

T1 - BCG Vaccination Induces Long-Term Functional Reprogramming of Human Neutrophils

AU - Moorlag, Simone J.C.F.M.

AU - Rodriguez-Rosales, Yessica Alina

AU - Gillard, Joshua

AU - Fanucchi, Stephanie

AU - Theunissen, Kate

AU - Novakovic, Boris

AU - De Bont, Cynthia M.

AU - Negishi, Yutaka

AU - Fok, Ezio T.

AU - Kalafati, Lydia

AU - Verginis, Panayotis

AU - Mourits, Vera P.

AU - Koeken, Valerie A.C.M.

AU - De Bree, L. Charlotte J.

AU - Pruijn, Ger J.M.

AU - Fenwick, Craig

AU - Van Crevel, Reinout

AU - Joosten, Leo A.B.

AU - Joosten, Irma

AU - Koenen, Hans

AU - Mhlanga, Musa M.

AU - Diavatopoulos, Dimitri A.

AU - Chavakis, Triantafyllos

AU - Netea, Mihai G.

PY - 2020/11/17

Y1 - 2020/11/17

N2 - SummaryThe 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.

AB - SummaryThe 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.

KW - innate immune memory

KW - trained immunity

KW - neutrophil

KW - polymorphonuclear leukocytes

KW - BCG

KW - nonspecific effects of vaccines

KW - epigenetics

U2 - 10.1016/j.celrep.2020.108387

DO - 10.1016/j.celrep.2020.108387

M3 - Article

VL - 33

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 7

M1 - 108387

ER -

BCG Vaccination Induces Long-Term Functional Reprogramming of Human Neutrophils

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Keywords

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Triantafyllos Chavakis

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