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J Infect Dis. 2019 Apr 8. pii: jiz147. doi: 10.1093/infdis/jiz147. [Epub ahead of print]

Early clearance of Mycobacterium tuberculosis is associated with increased innate immune responses.

Author information

1
Department of Pathology and Molecular Medicine, University of Otago, Wellington, New Zealand.
2
Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
3
TB-HIV Research Center, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia.
4
Department of Internal Medicine, Faculty of Medicine, Universitas Padajdaran, Hasan Sadikin Hospital, Bandung, Indonesia.
5
Department of Public Health, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia.
6
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboudumc, Nijmegen, The Netherlands.
7
Department of Haematology, Radboudumc, Nijmegen, The Netherlands.
8
Department of Clinical Pathology, Faculty of Medicine, Universitas Padjadjaran, Hasan Sadikin Hospital, Bandung, Indonesia.
9
Human Genomics Laboratory, Craiova University of Medicine and Pharmacy, Craiova, Romania.
10
Department of Mathematics and Statistics, University of Otago, Dunedin, New Zealand.
11
Centre for International Health, Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand.

Abstract

INTRODUCTION:

A proportion of tuberculosis (TB) case contacts do not become infected, even when heavily exposed. We studied the innate immune responses of TB case contacts to understand their role in protection against infection with Mycobacterium tuberculosis, termed 'early clearance'.

METHODS:

Indonesian household contacts of TB cases were tested for interferon-γ release assay (IGRA) conversion between baseline and 14 weeks post-recruitment. Blood cell populations and ex-vivo innate whole blood cytokine responses were measured at baseline and, in a subgroup, flow cytometry was performed at weeks 2 and 14. Immunological characteristics were measured for early clearers, defined as a persistently negative IGRA at 3 months, and converters, whose IGRA converted from negative to positive.

RESULTS:

Among 1347 case contacts, 317 were early clearers and 116 converters. Flow cytometry showed a resolving innate cellular response from 2 to 14 weeks in persistently IGRA negative contacts but not converters. There were no differences in cytokine responses to mycobacterial stimuli, but compared to converters, persistently IGRA negative contacts produced more proinflammatory cytokines following heterologous stimulation with Escherichia coli and Streptococcus pneumoniae.

CONCLUSIONS:

Early clearance of M. tuberculosis is associated with enhanced heterologous innate immune responses similar to those activated during induction of trained immunity.

KEYWORDS:

BCG vaccine; MAIT cells; Mycobacterium tuberculosis infection; early clearance; iNKT cells; monocytes; neutrophils; trained innate immunity; γδ T cells

PMID:
30958547
DOI:
10.1093/infdis/jiz147

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