Research ArticleImmunologyInfectious disease Open Access | 10.1172/jci.insight.195866

Dearbhla M. Murphy,1 Isabella Batten,1 Aoife O’Farrell,2 Simon R. Carlile,3 Sinead A. O’Rourke,3 Chloe Court,1 Brenda Morris,3 Gina Leisching,1 Gráinne Jameson,1 Sarah A. Connolly,1 Adam H. Dyer,1 John P. McGrath,1 Emma McNally,1,4 Olivia Sandby-Thomas,1 Anjali Yennemadi,1 Conor M. Finlay,1 Clíona Ní Cheallaigh,1 Jean Dunne,1,5 Cilian Ó Maoldomhnaigh,1 Laura E. Gleeson,1,4 Aisling Dunne,3 Nollaig Bourke,1 Reinout van Crevel,6 Donal J. Cox,1 Niall Conlon,1,5 Arjun Raj,2,7 Rachel M. McLoughlin,3 Joseph Keane,1,4 and Sharee A. Basdeo1

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Murphy, D. in: PubMed | Google Scholar |

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Batten, I. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by O’Farrell, A. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Carlile, S. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by O’Rourke, S. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Court, C. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Morris, B. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Leisching, G. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Jameson, G. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Connolly, S. in: PubMed | Google Scholar |

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Dyer, A. in: PubMed | Google Scholar |

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by McGrath, J. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by McNally, E. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Sandby-Thomas, O. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Yennemadi, A. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Finlay, C. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Cheallaigh, C. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Dunne, J. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Maoldomhnaigh, C. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Gleeson, L. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Dunne, A. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Bourke, N. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by van Crevel, R. in: PubMed | Google Scholar |

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Cox, D. in: PubMed | Google Scholar |

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Conlon, N. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Raj, A. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by McLoughlin, R. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Keane, J. in: PubMed | Google Scholar

1School of Medicine, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.

2Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.

4National Tuberculosis Centre, Department of Respiratory Medicine, and

5Department of Clinical Immunology, St. James’s Hospital, Dublin, Ireland.

6Department of Internal Medicine and Radboud Community for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

7Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Address correspondence to: Sharee A. Basdeo, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St James’s Hospital, Trinity College Dublin, The University of Dublin, James’s Street, Dublin 8, Ireland, D08W9RT. Phone: 353.1.8963266; Email: basdeos@tcd.ie.

Find articles by Basdeo, S. in: PubMed | Google Scholar |

Published February 10, 2026 - More info

Published in Volume 11, Issue 6 on March 23, 2026
JCI Insight. 2026;11(6):e195866. https://doi.org/10.1172/jci.insight.195866.
© 2026 Murphy et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Published February 10, 2026 - Version history
Received: May 30, 2025; Accepted: February 4, 2026 View PDF Abstract

Infectious diseases remain a global health challenge, driven by increasing antimicrobial resistance and the threat of emerging epidemics. Mycobacterium tuberculosis and Staphylococcus aureus are leading causes of mortality worldwide. Trained immunity — a form of innate immune memory — offers a promising approach to enhance pathogen clearance. Here, we demonstrate that IFN-γ induces trained immunity in human monocytes through a mechanism involving mTORC1 activation, glutaminolysis, and epigenetic remodeling. Macrophages derived from IFN-γ–trained monocytes exhibited increased glycolytic activity with enhanced cytokine and chemokine responses upon stimulation or infection. Crucially, trained macrophages had increased production of reactive oxygen species, which mediated enhanced bactericidal activity against methicillin-resistant S. aureus and M. tuberculosis. Furthermore, ATAC-sequencing analysis of IFN-γ–trained macrophages revealed increased chromatin accessibility in regions associated with host defense. Last, IFN-γ training restored impaired innate responses in macrophages from individuals homozygous for the TIRAP 180L polymorphism, a genetic variant associated with increased susceptibility to infection. These findings establish IFN-γ as a potent inducer of trained immunity in human monocytes and support its potential as a host-directed strategy to strengthen antimicrobial defenses, particularly in genetically susceptible individuals and high-risk clinical contexts.

Graphical Abstract Introduction

Trained immunity metabolically and epigenetically reprograms innate immune cells, altering their response to pathogens (1–