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Front Immunol. 2018 Apr 30;9:869. doi: 10.3389/fimmu.2018.00869. eCollection 2018.
Bacillus Calmette-Gu?rin-Induced Trained Immunity Is Not Protective for Experimental Influenza A/Anhui/1/2013 (H7N9) Infection in Mice.
de Bree CLCJ1,2,3,4, Marijnissen RJ5, Kel JM5, Rosendahl Huber SK5, Aaby P3, Benn CS3,4, Wijnands MVW5, Diavatopoulos DA2,6, van Crevel R1,2, Joosten LAB1,2, Netea MG1,2,7, Dulos J8.
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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?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?rin; innate immune memory; oseltamivir; trained immunity
PMID: 29760700 PMCID: PMC5936970 DOI: 10.3389/fimmu.2018.00869
Free PMC Article
Bacillus Calmette-Gu?rin-Induced Trained Immunity Is Not Protective for Experimental Influenza A/Anhui/1/2013 (H7N9) Infection in Mice.
de Bree CLCJ1,2,3,4, Marijnissen RJ5, Kel JM5, Rosendahl Huber SK5, Aaby P3, Benn CS3,4, Wijnands MVW5, Diavatopoulos DA2,6, van Crevel R1,2, Joosten LAB1,2, Netea MG1,2,7, Dulos J8.
Author information
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?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?rin; innate immune memory; oseltamivir; trained immunity
PMID: 29760700 PMCID: PMC5936970 DOI: 10.3389/fimmu.2018.00869
Free PMC Article