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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Elsevier
2023-05-01
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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. |
first_indexed | 2024-03-13T07:57:10Z |
format | Article |
id | doaj.art-8534b02c1bcf4e559287bfdff91c0299 |
institution | Directory Open Access Journal |
issn | 1201-9712 |
language | English |
last_indexed | 2024-03-13T07:57:10Z |
publishDate | 2023-05-01 |
publisher | Elsevier |
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series | International Journal of Infectious Diseases |
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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