Innate and Adaptive Immune Responses during Acute M. tuberculosis Infection in Adult Household Contacts in Kampala, Uganda

C. Scott Mahan Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio; Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda; Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, Ohio; Departments of Medicine and Microbiology, Makerere University College of Medical Sciences, Kampala, Uganda; Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia; Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals-Case Medical Center, Cleveland, Ohio, for the Tuberculosis Research Unit (TBRU)

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Sarah Zalwango Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio; Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda; Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, Ohio; Departments of Medicine and Microbiology, Makerere University College of Medical Sciences, Kampala, Uganda; Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia; Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals-Case Medical Center, Cleveland, Ohio, for the Tuberculosis Research Unit (TBRU)

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Bonnie A. Thiel Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio; Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda; Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, Ohio; Departments of Medicine and Microbiology, Makerere University College of Medical Sciences, Kampala, Uganda; Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia; Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals-Case Medical Center, Cleveland, Ohio, for the Tuberculosis Research Unit (TBRU)

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LaShaunda L. Malone Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio; Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda; Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, Ohio; Departments of Medicine and Microbiology, Makerere University College of Medical Sciences, Kampala, Uganda; Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia; Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals-Case Medical Center, Cleveland, Ohio, for the Tuberculosis Research Unit (TBRU)

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Keith A. Chervenak Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio; Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda; Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, Ohio; Departments of Medicine and Microbiology, Makerere University College of Medical Sciences, Kampala, Uganda; Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia; Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals-Case Medical Center, Cleveland, Ohio, for the Tuberculosis Research Unit (TBRU)

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Joy Baseke Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio; Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda; Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, Ohio; Departments of Medicine and Microbiology, Makerere University College of Medical Sciences, Kampala, Uganda; Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia; Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals-Case Medical Center, Cleveland, Ohio, for the Tuberculosis Research Unit (TBRU)

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Dennis Dobbs Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio; Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda; Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, Ohio; Departments of Medicine and Microbiology, Makerere University College of Medical Sciences, Kampala, Uganda; Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia; Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals-Case Medical Center, Cleveland, Ohio, for the Tuberculosis Research Unit (TBRU)

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Catherine M. Stein Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio; Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda; Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, Ohio; Departments of Medicine and Microbiology, Makerere University College of Medical Sciences, Kampala, Uganda; Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia; Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals-Case Medical Center, Cleveland, Ohio, for the Tuberculosis Research Unit (TBRU)

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Harriet Mayanja Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio; Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda; Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, Ohio; Departments of Medicine and Microbiology, Makerere University College of Medical Sciences, Kampala, Uganda; Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia; Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals-Case Medical Center, Cleveland, Ohio, for the Tuberculosis Research Unit (TBRU)

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Moses Joloba Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio; Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda; Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, Ohio; Departments of Medicine and Microbiology, Makerere University College of Medical Sciences, Kampala, Uganda; Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia; Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals-Case Medical Center, Cleveland, Ohio, for the Tuberculosis Research Unit (TBRU)

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Christopher C. Whalen Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio; Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda; Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, Ohio; Departments of Medicine and Microbiology, Makerere University College of Medical Sciences, Kampala, Uganda; Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia; Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals-Case Medical Center, Cleveland, Ohio, for the Tuberculosis Research Unit (TBRU)

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W. Henry Boom Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio; Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda; Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, Ohio; Departments of Medicine and Microbiology, Makerere University College of Medical Sciences, Kampala, Uganda; Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia; Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals-Case Medical Center, Cleveland, Ohio, for the Tuberculosis Research Unit (TBRU)

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Contacts of active pulmonary tuberculosis (TB) patients are at risk for Mycobacterium tuberculosis (MTB) infection. Because most infections are controlled, studies during MTB infection provide insight into protective immunity. We compared immune responses of adult household contacts that did and did not convert the tuberculin skin test (TST). Innate and adaptive immune responses were measured by whole blood assay. Responses of TST converters (TSTC) were compared with persistently TST negative contacts (PTST–) and contacts who were TST+ at baseline (TST+). TLR-2, TLR-4, and IFN-γR responses to IFN-γ did not differ between the groups, nor did γδ T cell responses. T cell responses to MTB antigens differed markedly among TSTC, PTST–, and TST+ contacts. Thus, no differences in innate responses were found among the three household contact groups. However, adaptive T cell responses to MTB antigens did differ before and during MTB infection among PTST–, TSTC, and TST+ contacts.

Author Notes

*Address correspondence to C. Scott Mahan, Department of Medicine/Division of Infectious Diseases, MetroHealth Medical Center, 2500 MetroHealth Drive, Cleveland, OH 44109. E-mail: csmahan@gmail.com

Financial support: This project has been funded in whole by the Tuberculosis Research Unit (TBRU), established with Federal funds from the United States National Institutes of Allergy and Infectious Diseases and the United States National Institutes of Health and Human Services, under contract no. HHSN266200700022C/NO1-AI-70022 and N01-AI-95383.

Authors' addresses: C. Scott Mahan, MetroHealth Medical Center, Cleveland, OH, E-mail: csmahan@gmail.com. Sarah Zalwango, Joy Baseke, Dennis Dobbs, Harriet Mayanja, and Moses Joloba, Tuberculosis Research Unit, Case Western Reserve University, Cleveland, OH, and Uganda-CWRU Research Collaboration, Kampala, Uganda, E-mails: szalwango@mucwru.org, basekejoy@yahoo.com, dennisdobbs@gmail.com, hmk@mucwru.or.ug, and immuno@jcrc.co.ug. Bonnie A. Thiel, LaShaunda L. Malone, Keith A. Chervenak, Catherine M. Stein, and W. Henry Boom, Tuberculosis Research Unit, Case Western Reserve University, Cleveland, OH, E-mails: bat2@case.edu, llm19@case.edu, kac2@case.edu, catherine.stein@case.edu, and whb@case.edu. Christopher C. Whalen, Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, GA, E-mail: ccwhalen@uga.edu.

Reprint requests: C. Scott Mahan, Department of Medicine/Division of Infectious Diseases, MetroHealth Medical Center, 2500 MetroHealth Drive, Cleveland, OH 44109; Tel: 216-778-7829; Fax: 216-778-8877; E-mail: csmahan@gmail.com.

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