Monocyte Transcriptional Responses to Mycobacterium tuberculosis Associate with Resistance to Tuberculin Skin Test and Interferon Gamma Release Assay Conversion

Author:

Simmons Jason D.1ORCID,Dill-McFarland Kimberly A.1,Stein Catherine M.23,Van Phu T.4,Chihota Violet56,Ntshiqa Thobani6,Maenetje Pholo6,Peterson Glenna J.1,Benchek Penelope2,Nsereko Mary7,Velen Kavindhran6,Fielding Katherine L.58,Grant Alison D.589,Gottardo Raphael41011,Mayanja-Kizza Harriet12,Wallis Robert S.6,Churchyard Gavin5613,Boom W. Henry3,Hawn Thomas R.1

Affiliation:

1. TB Research & Training Center, Department of Medicine, University of Washington, Seattle, Washington, USA

2. Department of Population & Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA

3. Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA

4. Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

5. School of Public Health, University of Witwatersrand, Johannesburg, South Africa

6. The Aurum Institute, Parktown, South Africa

7. Uganda-CWRU Research Collaboration, Kampala, Uganda

8. TB Centre, London School of Hygiene & Tropical Medicine, London, United Kingdom

9. Africa Health Research Institute, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa

10. University of Lausanne and Lausanne University Hospital, Lausanne, Switzerland

11. Swiss Institute of Bioinformatics, Lausanne, Switzerland

12. Department of Medicine, School of Medicine, Makerere University, Kampala, Uganda

13. Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA

Abstract

After heavy M. tuberculosis exposure, the events that determine why some individuals resist TST/IGRA conversion are poorly defined. Enrichment of the TNF signaling gene set among RSTR monocytes from multiple distinct cohorts suggests an important role for the monocyte TNF response in determining this alternative immune outcome.

Funder

HHS | National Institutes of Health

Bill and Melinda Gates Foundation

South African Medical Research Council

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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