The impact of sex hormones on BCG-induced trained immunity

Charlotte L.C.J. de Bree, Robine Janssen, Peter Aaby, Reinout van Crevel, Leo A.B. Joosten, Christine Stabell Benn, Mihai G. Netea*

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

The anti-tuberculosis vaccine Bacillus Calmette-Guérin (BCG) is a well-known immune modulator that induces nonspecific protective effects against heterologous infections through induction of innate immune memory, also termed “trained immunity.” In randomized trials in low weight newborns, BCG vaccination reduced neonatal mortality due to decreased incidence of sepsis and respiratory infections. In many studies, sex-differential nonspecific effects of vaccines have been observed, but the mechanisms behind these differential effects are unknown. We investigated whether the important sex hormones estrogen and dihydrotestosterone (DHT) influence BCG-induced trained immunity in human primary monocytes. Although addition of estradiol and DHT to BCG inhibited the production of proinflammatory cytokines after direct stimulation of human monocytes, they did not influence the induction of trained immunity by BCG. In addition, estradiol or DHT did not induce training or tolerance in monocytes themselves. We conclude that these important sex hormones are unlikely to explain the sex-differential effects after BCG vaccination. Future studies should focus on the investigation of alternative mechanisms as an explanation for sex-differential nonspecific effects of BCG vaccination.

OriginalsprogEngelsk
TidsskriftJournal of Leukocyte Biology
Vol/bind104
Udgave nummer3
Sider (fra-til)573-578
ISSN0741-5400
DOI
StatusUdgivet - 1. sep. 2018

Fingeraftryk

Estrogens
Weights and Measures
Incidence

Citer dette

de Bree, Charlotte L.C.J. ; Janssen, Robine ; Aaby, Peter ; van Crevel, Reinout ; Joosten, Leo A.B. ; Benn, Christine Stabell ; Netea, Mihai G. / The impact of sex hormones on BCG-induced trained immunity. I: Journal of Leukocyte Biology. 2018 ; Bind 104, Nr. 3. s. 573-578.
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title = "The impact of sex hormones on BCG-induced trained immunity",
abstract = "The anti-tuberculosis vaccine Bacillus Calmette-Gu{\'e}rin (BCG) is a well-known immune modulator that induces nonspecific protective effects against heterologous infections through induction of innate immune memory, also termed “trained immunity.” In randomized trials in low weight newborns, BCG vaccination reduced neonatal mortality due to decreased incidence of sepsis and respiratory infections. In many studies, sex-differential nonspecific effects of vaccines have been observed, but the mechanisms behind these differential effects are unknown. We investigated whether the important sex hormones estrogen and dihydrotestosterone (DHT) influence BCG-induced trained immunity in human primary monocytes. Although addition of estradiol and DHT to BCG inhibited the production of proinflammatory cytokines after direct stimulation of human monocytes, they did not influence the induction of trained immunity by BCG. In addition, estradiol or DHT did not induce training or tolerance in monocytes themselves. We conclude that these important sex hormones are unlikely to explain the sex-differential effects after BCG vaccination. Future studies should focus on the investigation of alternative mechanisms as an explanation for sex-differential nonspecific effects of BCG vaccination.",
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author = "{de Bree}, {Charlotte L.C.J.} and Robine Janssen and Peter Aaby and {van Crevel}, Reinout and Joosten, {Leo A.B.} and Benn, {Christine Stabell} and Netea, {Mihai G.}",
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de Bree, CLCJ, Janssen, R, Aaby, P, van Crevel, R, Joosten, LAB, Benn, CS & Netea, MG 2018, 'The impact of sex hormones on BCG-induced trained immunity', Journal of Leukocyte Biology, bind 104, nr. 3, s. 573-578. https://doi.org/10.1002/JLB.5MA0118-027R

The impact of sex hormones on BCG-induced trained immunity. / de Bree, Charlotte L.C.J.; Janssen, Robine; Aaby, Peter; van Crevel, Reinout; Joosten, Leo A.B.; Benn, Christine Stabell; Netea, Mihai G.

I: Journal of Leukocyte Biology, Bind 104, Nr. 3, 01.09.2018, s. 573-578.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - The impact of sex hormones on BCG-induced trained immunity

AU - de Bree, Charlotte L.C.J.

AU - Janssen, Robine

AU - Aaby, Peter

AU - van Crevel, Reinout

AU - Joosten, Leo A.B.

AU - Benn, Christine Stabell

AU - Netea, Mihai G.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - The anti-tuberculosis vaccine Bacillus Calmette-Guérin (BCG) is a well-known immune modulator that induces nonspecific protective effects against heterologous infections through induction of innate immune memory, also termed “trained immunity.” In randomized trials in low weight newborns, BCG vaccination reduced neonatal mortality due to decreased incidence of sepsis and respiratory infections. In many studies, sex-differential nonspecific effects of vaccines have been observed, but the mechanisms behind these differential effects are unknown. We investigated whether the important sex hormones estrogen and dihydrotestosterone (DHT) influence BCG-induced trained immunity in human primary monocytes. Although addition of estradiol and DHT to BCG inhibited the production of proinflammatory cytokines after direct stimulation of human monocytes, they did not influence the induction of trained immunity by BCG. In addition, estradiol or DHT did not induce training or tolerance in monocytes themselves. We conclude that these important sex hormones are unlikely to explain the sex-differential effects after BCG vaccination. Future studies should focus on the investigation of alternative mechanisms as an explanation for sex-differential nonspecific effects of BCG vaccination.

AB - The anti-tuberculosis vaccine Bacillus Calmette-Guérin (BCG) is a well-known immune modulator that induces nonspecific protective effects against heterologous infections through induction of innate immune memory, also termed “trained immunity.” In randomized trials in low weight newborns, BCG vaccination reduced neonatal mortality due to decreased incidence of sepsis and respiratory infections. In many studies, sex-differential nonspecific effects of vaccines have been observed, but the mechanisms behind these differential effects are unknown. We investigated whether the important sex hormones estrogen and dihydrotestosterone (DHT) influence BCG-induced trained immunity in human primary monocytes. Although addition of estradiol and DHT to BCG inhibited the production of proinflammatory cytokines after direct stimulation of human monocytes, they did not influence the induction of trained immunity by BCG. In addition, estradiol or DHT did not induce training or tolerance in monocytes themselves. We conclude that these important sex hormones are unlikely to explain the sex-differential effects after BCG vaccination. Future studies should focus on the investigation of alternative mechanisms as an explanation for sex-differential nonspecific effects of BCG vaccination.

KW - Bacillus Calmette-Guérin

KW - dihydrotestosterone

KW - estradiol

KW - heterologous protection

KW - innate immune memory

KW - sex-differential effects

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DO - 10.1002/JLB.5MA0118-027R

M3 - Journal article

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VL - 104

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JO - Journal of Leukocyte Biology

JF - Journal of Leukocyte Biology

SN - 0741-5400

IS - 3

ER -