Newborn bacille Calmette-Guérin vaccination induces robust infant interferon-γ-expressing natural killer cell responses to mycobacteria

Objectives: The bacille Calmette-Guérin (BCG) vaccine is usually administered at birth to protect against severe forms of tuberculosis in children. BCG also confers some protection against other infections, possibly mediated by innate immune training. We investigated whether newborn BCG vaccination...

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Main Authors: Melissa Murphy, Sara Suliman, Libby Briel, Helen Veldtsman, Nondumiso Khomba, Hadn Africa, Marcia Steyn, Candice I. Snyders, Ilana C. van Rensburg, Gerhard Walzl, Novel N. Chegou, Mark Hatherill, Willem A. Hanekom, Thomas J. Scriba, Elisa Nemes
Format: Article
Language:English
Published: Elsevier 2023-05-01
Series:International Journal of Infectious Diseases
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Online Access:http://www.sciencedirect.com/science/article/pii/S1201971223000693
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author Melissa Murphy
Sara Suliman
Libby Briel
Helen Veldtsman
Nondumiso Khomba
Hadn Africa
Marcia Steyn
Candice I. Snyders
Ilana C. van Rensburg
Gerhard Walzl
Novel N. Chegou
Mark Hatherill
Willem A. Hanekom
Thomas J. Scriba
Elisa Nemes
author_facet Melissa Murphy
Sara Suliman
Libby Briel
Helen Veldtsman
Nondumiso Khomba
Hadn Africa
Marcia Steyn
Candice I. Snyders
Ilana C. van Rensburg
Gerhard Walzl
Novel N. Chegou
Mark Hatherill
Willem A. Hanekom
Thomas J. Scriba
Elisa Nemes
author_sort Melissa Murphy
collection DOAJ
description Objectives: The bacille Calmette-Guérin (BCG) vaccine is usually administered at birth to protect against severe forms of tuberculosis in children. BCG also confers some protection against other infections, possibly mediated by innate immune training. We investigated whether newborn BCG vaccination modulates myeloid and natural killer (NK) cell responses to mycobacteria. Methods: BCG vaccination was either administered at birth or delayed to 6 or 10 weeks of age in 130 South African infants. Whole blood was stimulated with BCG and clusters of differentiation (CD)4+ T, myeloid, and NK cell responses were measured by flow cytometry; the levels of secreted cytokines were measured by a multiplex bead array. Results: Newborn BCG vaccination was associated with significantly higher frequencies of BCG-reactive, cytokine-expressing CD4+ T cells, and interferon (IFN)-γ-expressing NK cells than in unvaccinated infants but no differences in cytokine-expressing CD33+ myeloid cells were observed. The induction of BCG-reactive IFN-γ-expressing NK cells was not associated with the markers of NK cell maturation, differentiation, or cytokine receptor expression. BCG-reactive NK cell responses correlated directly with the levels of secreted interleukin (IL)-2 and IFN-γ and the innate pro-inflammatory cytokines IL-6, IL-1β, and tumor necrosis factor (TNF) in BCG-vaccinated infants only. Conclusion: We showed that BCG-reactive IFN-γ-expressing NK cells are strongly induced by BCG vaccination in infants and are likely amplified through bystander cytokines.
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spelling doaj.art-8534b02c1bcf4e559287bfdff91c02992023-06-02T04:22:41ZengElsevierInternational Journal of Infectious Diseases1201-97122023-05-01130S52S62Newborn bacille Calmette-Guérin vaccination induces robust infant interferon-γ-expressing natural killer cell responses to mycobacteriaMelissa Murphy0Sara Suliman1Libby Briel2Helen Veldtsman3Nondumiso Khomba4Hadn Africa5Marcia Steyn6Candice I. Snyders7Ilana C. van Rensburg8Gerhard Walzl9Novel N. Chegou10Mark Hatherill11Willem A. Hanekom12Thomas J. Scriba13Elisa Nemes14South African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South AfricaSouth African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South AfricaSouth African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South AfricaSouth African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South AfricaSouth African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South AfricaSouth African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South AfricaSouth African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South AfricaDepartment of Science and Technology, National Research Foundation, Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaDepartment of Science and Technology, National Research Foundation, Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaDepartment of Science and Technology, National Research Foundation, Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaDepartment of Science and Technology, National Research Foundation, Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaSouth African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South AfricaSouth African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South AfricaSouth African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South AfricaSouth African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South Africa; Corresponding author:Objectives: The bacille Calmette-Guérin (BCG) vaccine is usually administered at birth to protect against severe forms of tuberculosis in children. BCG also confers some protection against other infections, possibly mediated by innate immune training. We investigated whether newborn BCG vaccination modulates myeloid and natural killer (NK) cell responses to mycobacteria. Methods: BCG vaccination was either administered at birth or delayed to 6 or 10 weeks of age in 130 South African infants. Whole blood was stimulated with BCG and clusters of differentiation (CD)4+ T, myeloid, and NK cell responses were measured by flow cytometry; the levels of secreted cytokines were measured by a multiplex bead array. Results: Newborn BCG vaccination was associated with significantly higher frequencies of BCG-reactive, cytokine-expressing CD4+ T cells, and interferon (IFN)-γ-expressing NK cells than in unvaccinated infants but no differences in cytokine-expressing CD33+ myeloid cells were observed. The induction of BCG-reactive IFN-γ-expressing NK cells was not associated with the markers of NK cell maturation, differentiation, or cytokine receptor expression. BCG-reactive NK cell responses correlated directly with the levels of secreted interleukin (IL)-2 and IFN-γ and the innate pro-inflammatory cytokines IL-6, IL-1β, and tumor necrosis factor (TNF) in BCG-vaccinated infants only. Conclusion: We showed that BCG-reactive IFN-γ-expressing NK cells are strongly induced by BCG vaccination in infants and are likely amplified through bystander cytokines.http://www.sciencedirect.com/science/article/pii/S1201971223000693NK cells, Myeloid cellsBCG vaccinationInfantTuberculosis
spellingShingle Melissa Murphy
Sara Suliman
Libby Briel
Helen Veldtsman
Nondumiso Khomba
Hadn Africa
Marcia Steyn
Candice I. Snyders
Ilana C. van Rensburg
Gerhard Walzl
Novel N. Chegou
Mark Hatherill
Willem A. Hanekom
Thomas J. Scriba
Elisa Nemes
Newborn bacille Calmette-Guérin vaccination induces robust infant interferon-γ-expressing natural killer cell responses to mycobacteria
International Journal of Infectious Diseases
NK cells, Myeloid cells
BCG vaccination
Infant
Tuberculosis
title Newborn bacille Calmette-Guérin vaccination induces robust infant interferon-γ-expressing natural killer cell responses to mycobacteria
title_full Newborn bacille Calmette-Guérin vaccination induces robust infant interferon-γ-expressing natural killer cell responses to mycobacteria
title_fullStr Newborn bacille Calmette-Guérin vaccination induces robust infant interferon-γ-expressing natural killer cell responses to mycobacteria
title_full_unstemmed Newborn bacille Calmette-Guérin vaccination induces robust infant interferon-γ-expressing natural killer cell responses to mycobacteria
title_short Newborn bacille Calmette-Guérin vaccination induces robust infant interferon-γ-expressing natural killer cell responses to mycobacteria
title_sort newborn bacille calmette guerin vaccination induces robust infant interferon γ expressing natural killer cell responses to mycobacteria
topic NK cells, Myeloid cells
BCG vaccination
Infant
Tuberculosis
url http://www.sciencedirect.com/science/article/pii/S1201971223000693
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