Bacillus Calmette-Guérin-Induced trained immunity is not protective for experimental influenza A/Anhui/1/2013 (H7N9) infection in mice

L. Charlotte J. de Bree, Renoud J. Marijnissen*, Junda M. Kel, Sietske K.Rosendahl Huber, Peter Aaby, Christine Stabell Benn, Marcel V.W. Wijnands, Dimitri A. Diavatopoulos, Reinout van Crevel, Leo A.B. Joosten, Mihai G. Netea, John Dulos

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Resumé

Avian influenza A of the subtype H7N9 has been responsible for almost 1,600 confirmed human infections and more than 600 deaths since its first outbreak in 2013. Although sustained human-to-human transmission has not been reported yet, further adaptations to humans in the viral genome could potentially lead to an influenza pandemic, which may have severe consequences due to the absence of pre-existent immunity to this strain at population level. Currently there is no influenza A (H7N9) vaccine available. Therefore, in case of a pandemic outbreak, alternative preventive approaches are needed, ideally even independent of the type of influenza virus outbreak. Bacillus Calmette-Guérin (BCG) is known to induce strong heterologous immunological effects, and it has been shown that BCG protects against non-related infection challenges in several mouse models. BCG immunization of mice as well as human induces trained innate immune responses, resulting in increased cytokine responses upon subsequent ex vivo peripheral blood mononuclear cell restimulation. We investigated whether BCG (Statens Serum Institut-Denmark)-induced trained immunity may protect against a lethal avian influenza A/Anhui/1/2013 (H7N9) challenge. Here, we show that isolated splenocytes as well as peritoneal macrophages of BCG-immunized BALB/c mice displayed a trained immunity phenotype resulting in increased innate cytokine responses upon ex vivo restimulation. However, after H7N9 infection, no significant differences were found between the BCG immunized and the vehicle control group at the level of survival, weight loss, pulmonary influenza A nucleoprotein staining, or histopathology. In conclusion, BCG-induced trained immunity did not result in protection in an oseltamivir-sensitive influenza A/Anhui/1/2013 (H7N9) challenge mouse model.

OriginalsprogEngelsk
Artikelnummer869
TidsskriftFrontiers in Immunology
Vol/bind9
Udgave nummerAPR
Antal sider11
ISSN1664-3224
DOI
StatusUdgivet - 2018

Fingeraftryk

Human Influenza
Disease Outbreaks
Influenza in Birds
Nucleoproteins
Peritoneal Macrophages
Denmark
Orthomyxoviridae
Lung
Control Groups
Serum
Population

Citer dette

J. de Bree, L. Charlotte ; Marijnissen, Renoud J. ; Kel, Junda M. ; Huber, Sietske K.Rosendahl ; Aaby, Peter ; Benn, Christine Stabell ; Wijnands, Marcel V.W. ; Diavatopoulos, Dimitri A. ; Crevel, Reinout van ; Joosten, Leo A.B. ; Netea, Mihai G. ; Dulos, John. / Bacillus Calmette-Guérin-Induced trained immunity is not protective for experimental influenza A/Anhui/1/2013 (H7N9) infection in mice. I: Frontiers in Immunology. 2018 ; Bind 9, Nr. APR.
@article{074568bf65614d85875bb51854888bc3,
title = "Bacillus Calmette-Gu{\'e}rin-Induced trained immunity is not protective for experimental influenza A/Anhui/1/2013 (H7N9) infection in mice",
abstract = "Avian influenza A of the subtype H7N9 has been responsible for almost 1,600 confirmed human infections and more than 600 deaths since its first outbreak in 2013. Although sustained human-to-human transmission has not been reported yet, further adaptations to humans in the viral genome could potentially lead to an influenza pandemic, which may have severe consequences due to the absence of pre-existent immunity to this strain at population level. Currently there is no influenza A (H7N9) vaccine available. Therefore, in case of a pandemic outbreak, alternative preventive approaches are needed, ideally even independent of the type of influenza virus outbreak. Bacillus Calmette-Gu{\'e}rin (BCG) is known to induce strong heterologous immunological effects, and it has been shown that BCG protects against non-related infection challenges in several mouse models. BCG immunization of mice as well as human induces trained innate immune responses, resulting in increased cytokine responses upon subsequent ex vivo peripheral blood mononuclear cell restimulation. We investigated whether BCG (Statens Serum Institut-Denmark)-induced trained immunity may protect against a lethal avian influenza A/Anhui/1/2013 (H7N9) challenge. Here, we show that isolated splenocytes as well as peritoneal macrophages of BCG-immunized BALB/c mice displayed a trained immunity phenotype resulting in increased innate cytokine responses upon ex vivo restimulation. However, after H7N9 infection, no significant differences were found between the BCG immunized and the vehicle control group at the level of survival, weight loss, pulmonary influenza A nucleoprotein staining, or histopathology. In conclusion, BCG-induced trained immunity did not result in protection in an oseltamivir-sensitive influenza A/Anhui/1/2013 (H7N9) challenge mouse model.",
keywords = "Avian influenza A/Anhui/1/2013 (H7N9), Bacillus Calmette-Gu{\'e}rin, Innate immune memory, Oseltamivir, Trained immunity, Vaccination, Influenza Vaccines/immunology, Influenza A Virus, H7N9 Subtype/immunology, Orthomyxoviridae Infections/immunology, Animals, Female, Mice, Mice, Inbred BALB C, BCG Vaccine/immunology",
author = "{J. de Bree}, {L. Charlotte} and Marijnissen, {Renoud J.} and Kel, {Junda M.} and Huber, {Sietske K.Rosendahl} and Peter Aaby and Benn, {Christine Stabell} and Wijnands, {Marcel V.W.} and Diavatopoulos, {Dimitri A.} and Crevel, {Reinout van} and Joosten, {Leo A.B.} and Netea, {Mihai G.} and John Dulos",
year = "2018",
doi = "10.3389/fimmu.2018.00869",
language = "English",
volume = "9",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Research Foundation",
number = "APR",

}

J. de Bree, LC, Marijnissen, RJ, Kel, JM, Huber, SKR, Aaby, P, Benn, CS, Wijnands, MVW, Diavatopoulos, DA, Crevel, RV, Joosten, LAB, Netea, MG & Dulos, J 2018, 'Bacillus Calmette-Guérin-Induced trained immunity is not protective for experimental influenza A/Anhui/1/2013 (H7N9) infection in mice', Frontiers in Immunology, bind 9, nr. APR, 869. https://doi.org/10.3389/fimmu.2018.00869

Bacillus Calmette-Guérin-Induced trained immunity is not protective for experimental influenza A/Anhui/1/2013 (H7N9) infection in mice. / J. de Bree, L. Charlotte ; Marijnissen, Renoud J.; Kel, Junda M.; Huber, Sietske K.Rosendahl; Aaby, Peter; Benn, Christine Stabell; Wijnands, Marcel V.W.; Diavatopoulos, Dimitri A.; Crevel, Reinout van; Joosten, Leo A.B.; Netea, Mihai G.; Dulos, John.

I: Frontiers in Immunology, Bind 9, Nr. APR, 869, 2018.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Bacillus Calmette-Guérin-Induced trained immunity is not protective for experimental influenza A/Anhui/1/2013 (H7N9) infection in mice

AU - J. de Bree, L. Charlotte

AU - Marijnissen, Renoud J.

AU - Kel, Junda M.

AU - Huber, Sietske K.Rosendahl

AU - Aaby, Peter

AU - Benn, Christine Stabell

AU - Wijnands, Marcel V.W.

AU - Diavatopoulos, Dimitri A.

AU - Crevel, Reinout van

AU - Joosten, Leo A.B.

AU - Netea, Mihai G.

AU - Dulos, John

PY - 2018

Y1 - 2018

N2 - Avian influenza A of the subtype H7N9 has been responsible for almost 1,600 confirmed human infections and more than 600 deaths since its first outbreak in 2013. Although sustained human-to-human transmission has not been reported yet, further adaptations to humans in the viral genome could potentially lead to an influenza pandemic, which may have severe consequences due to the absence of pre-existent immunity to this strain at population level. Currently there is no influenza A (H7N9) vaccine available. Therefore, in case of a pandemic outbreak, alternative preventive approaches are needed, ideally even independent of the type of influenza virus outbreak. Bacillus Calmette-Guérin (BCG) is known to induce strong heterologous immunological effects, and it has been shown that BCG protects against non-related infection challenges in several mouse models. BCG immunization of mice as well as human induces trained innate immune responses, resulting in increased cytokine responses upon subsequent ex vivo peripheral blood mononuclear cell restimulation. We investigated whether BCG (Statens Serum Institut-Denmark)-induced trained immunity may protect against a lethal avian influenza A/Anhui/1/2013 (H7N9) challenge. Here, we show that isolated splenocytes as well as peritoneal macrophages of BCG-immunized BALB/c mice displayed a trained immunity phenotype resulting in increased innate cytokine responses upon ex vivo restimulation. However, after H7N9 infection, no significant differences were found between the BCG immunized and the vehicle control group at the level of survival, weight loss, pulmonary influenza A nucleoprotein staining, or histopathology. In conclusion, BCG-induced trained immunity did not result in protection in an oseltamivir-sensitive influenza A/Anhui/1/2013 (H7N9) challenge mouse model.

AB - Avian influenza A of the subtype H7N9 has been responsible for almost 1,600 confirmed human infections and more than 600 deaths since its first outbreak in 2013. Although sustained human-to-human transmission has not been reported yet, further adaptations to humans in the viral genome could potentially lead to an influenza pandemic, which may have severe consequences due to the absence of pre-existent immunity to this strain at population level. Currently there is no influenza A (H7N9) vaccine available. Therefore, in case of a pandemic outbreak, alternative preventive approaches are needed, ideally even independent of the type of influenza virus outbreak. Bacillus Calmette-Guérin (BCG) is known to induce strong heterologous immunological effects, and it has been shown that BCG protects against non-related infection challenges in several mouse models. BCG immunization of mice as well as human induces trained innate immune responses, resulting in increased cytokine responses upon subsequent ex vivo peripheral blood mononuclear cell restimulation. We investigated whether BCG (Statens Serum Institut-Denmark)-induced trained immunity may protect against a lethal avian influenza A/Anhui/1/2013 (H7N9) challenge. Here, we show that isolated splenocytes as well as peritoneal macrophages of BCG-immunized BALB/c mice displayed a trained immunity phenotype resulting in increased innate cytokine responses upon ex vivo restimulation. However, after H7N9 infection, no significant differences were found between the BCG immunized and the vehicle control group at the level of survival, weight loss, pulmonary influenza A nucleoprotein staining, or histopathology. In conclusion, BCG-induced trained immunity did not result in protection in an oseltamivir-sensitive influenza A/Anhui/1/2013 (H7N9) challenge mouse model.

KW - Avian influenza A/Anhui/1/2013 (H7N9)

KW - Bacillus Calmette-Guérin

KW - Innate immune memory

KW - Oseltamivir

KW - Trained immunity

KW - Vaccination

KW - Influenza Vaccines/immunology

KW - Influenza A Virus, H7N9 Subtype/immunology

KW - Orthomyxoviridae Infections/immunology

KW - Animals

KW - Female

KW - Mice

KW - Mice, Inbred BALB C

KW - BCG Vaccine/immunology

UR - https://doi.org/10.3389/fimmu.2018.02471

U2 - 10.3389/fimmu.2018.00869

DO - 10.3389/fimmu.2018.00869

M3 - Journal article

C2 - 29760700

AN - SCOPUS:85046642830

VL - 9

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

IS - APR

M1 - 869

ER -