Characterizing the BCG Induced Macrophage and Neutrophil Mechanisms for Defense Against Mycobacterium tuberculosis

The live attenuated Mycobacterium bovis strain, Bacille Calmette Guérin (BCG) is a potent innate immune stimulator. In the C57BL/6 mouse model of tuberculosis, BCG vaccination leads to a significant reduction of Mycobacterium tuberculosis burden after aerogenic infection. Our studies indicated that...

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Main Authors: Thomas E. Bickett, Jennifer McLean, Elizabeth Creissen, Linda Izzo, Cassidy Hagan, Antonio J. Izzo, Fabiola Silva Angulo, Angelo A. Izzo
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-06-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2020.01202/full
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author Thomas E. Bickett
Jennifer McLean
Elizabeth Creissen
Linda Izzo
Cassidy Hagan
Antonio J. Izzo
Fabiola Silva Angulo
Angelo A. Izzo
author_facet Thomas E. Bickett
Jennifer McLean
Elizabeth Creissen
Linda Izzo
Cassidy Hagan
Antonio J. Izzo
Fabiola Silva Angulo
Angelo A. Izzo
author_sort Thomas E. Bickett
collection DOAJ
description The live attenuated Mycobacterium bovis strain, Bacille Calmette Guérin (BCG) is a potent innate immune stimulator. In the C57BL/6 mouse model of tuberculosis, BCG vaccination leads to a significant reduction of Mycobacterium tuberculosis burden after aerogenic infection. Our studies indicated that BCG induced protection against pulmonary tuberculosis was independent of T cells and present as early as 7 days after vaccination. This protection showed longevity, as it did not wane when conventional T cell and TNF-α deficient mice were infected 30 days post-vaccination. As BCG induced mycobacterial killing after 7 days, this study investigated the contributions of the innate immune system after BCG vaccination to better understand mechanisms required for mycobacterial killing. Subcutaneous BCG inoculation resulted in significant CD11b+F4/80+ monocyte subset recruitment into the lungs within 7 days. Further studies revealed that killing of mycobacteria was dependent on the viability of BCG, because irradiated BCG did not have the same effect. Although others have identified BCG as a facilitator of trained innate immunity, we found that BCG reduced the mycobacterial burden in the absence of mechanisms required for trained innate immunity, highlighting a role for macrophages and neutrophils for vaccine induced killing of M. tuberculosis.
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spelling doaj.art-ab724926653d4b2286633affba82ccfe2022-12-21T23:00:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-06-011110.3389/fimmu.2020.01202524030Characterizing the BCG Induced Macrophage and Neutrophil Mechanisms for Defense Against Mycobacterium tuberculosisThomas E. BickettJennifer McLeanElizabeth CreissenLinda IzzoCassidy HaganAntonio J. IzzoFabiola Silva AnguloAngelo A. IzzoThe live attenuated Mycobacterium bovis strain, Bacille Calmette Guérin (BCG) is a potent innate immune stimulator. In the C57BL/6 mouse model of tuberculosis, BCG vaccination leads to a significant reduction of Mycobacterium tuberculosis burden after aerogenic infection. Our studies indicated that BCG induced protection against pulmonary tuberculosis was independent of T cells and present as early as 7 days after vaccination. This protection showed longevity, as it did not wane when conventional T cell and TNF-α deficient mice were infected 30 days post-vaccination. As BCG induced mycobacterial killing after 7 days, this study investigated the contributions of the innate immune system after BCG vaccination to better understand mechanisms required for mycobacterial killing. Subcutaneous BCG inoculation resulted in significant CD11b+F4/80+ monocyte subset recruitment into the lungs within 7 days. Further studies revealed that killing of mycobacteria was dependent on the viability of BCG, because irradiated BCG did not have the same effect. Although others have identified BCG as a facilitator of trained innate immunity, we found that BCG reduced the mycobacterial burden in the absence of mechanisms required for trained innate immunity, highlighting a role for macrophages and neutrophils for vaccine induced killing of M. tuberculosis.https://www.frontiersin.org/article/10.3389/fimmu.2020.01202/fullinnateBCG—Bacille Calmette-Guérin vaccinemacropahgemycobacerium tuberculosislung
spellingShingle Thomas E. Bickett
Jennifer McLean
Elizabeth Creissen
Linda Izzo
Cassidy Hagan
Antonio J. Izzo
Fabiola Silva Angulo
Angelo A. Izzo
Characterizing the BCG Induced Macrophage and Neutrophil Mechanisms for Defense Against Mycobacterium tuberculosis
Frontiers in Immunology
innate
BCG—Bacille Calmette-Guérin vaccine
macropahge
mycobacerium tuberculosis
lung
title Characterizing the BCG Induced Macrophage and Neutrophil Mechanisms for Defense Against Mycobacterium tuberculosis
title_full Characterizing the BCG Induced Macrophage and Neutrophil Mechanisms for Defense Against Mycobacterium tuberculosis
title_fullStr Characterizing the BCG Induced Macrophage and Neutrophil Mechanisms for Defense Against Mycobacterium tuberculosis
title_full_unstemmed Characterizing the BCG Induced Macrophage and Neutrophil Mechanisms for Defense Against Mycobacterium tuberculosis
title_short Characterizing the BCG Induced Macrophage and Neutrophil Mechanisms for Defense Against Mycobacterium tuberculosis
title_sort characterizing the bcg induced macrophage and neutrophil mechanisms for defense against mycobacterium tuberculosis
topic innate
BCG—Bacille Calmette-Guérin vaccine
macropahge
mycobacerium tuberculosis
lung
url https://www.frontiersin.org/article/10.3389/fimmu.2020.01202/full
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