The dynamics of immune responses to Mycobacterium tuberculosis during different stages of natural infection: A longitudinal study among Greenlanders

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Objective

Understanding human immunity to Mycobacterium tuberculosis ( Mtb) during different stages of infection is important for development of an effective tuberculosis (TB) vaccine. We aimed to evaluate immunity to Mtb infection by measuring immune responses to selected Mtb antigens expressed during different stages of infection over time and to observe sustainability of immunity.

Methods

In a cohort study comprising East Greenlanders aged 17–22 years (2012 to 2014) who had either; undetectable Mtb infection, ongoing or prior Mtb infection at enrolment, we measured immunity to 15 antigens over a one-year period. Quantiferon-TB Gold testing (QFT) defined Mtb infection status (undetected/detected). The eligible study population of East Greenlanders aged 17–22 years was identified from the entire population using the Civil Registration System. From the source population 65 participants were selected by stratified random sampling according to information on Mtb infection stage. Retrospective and prospective information on notified TB (including treatment) was obtained through the mandatory TB notification system and was used to characterise Mtb infection stage (ongoing/prior). Immunity to 15 antigens including two QFT antigens, PPD and 12 non-QFT antigens (representing early, constitutive and latent Mtb infection) was assessed by measuring immune responses using whole-blood antigen stimulation and interferon gamma measurement.

Results

Of 65 participants, 54 were considered Mtb-infected. Immunity to Mtb infection fluctuated with high annual risk of conversion (range: 6–69%) and reversion (range: 5–95%). During follow-up, five (8%) participants were notified with TB; neither conversion nor reversion was associated with an increased risk of progressing to TB.

Conclusions

Our findings suggest that human immunity to natural Mtb infection over time is versatile with fluctuations, resulting in high levels of conversion and reversion of immunity, thus human immunity to Mtb is much more dynamic than anticipated. The study findings suggest future use of longitudinal assessment of immune responses when searching for TB vaccine candidate antigens.

Related collections

Most cited references 36

Record: found
Abstract: found
Article: not found

Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling.

Joanna Betts, Pauline Lukey, Linda Robb … (2002)

The search for new TB drugs that rapidly and effectively sterilize the tissues and are thus able to shorten the duration of chemotherapy from the current 6 months has been hampered by a lack of understanding of the metabolism of the bacterium when in a 'persistent' or latent form. Little is known about the condition in which the bacilli survive, although laboratory models have shown that Mycobacterium tuberculosis can exist in a non-growing, drug-resistant state that may mimic persistence in vivo. Using nutrient starvation, we have established a model in which M. tuberculosis arrests growth, decreases its respiration rate and is resistant to isoniazid, rifampicin and metronidazole. We have used microarray and proteome analysis to investigate the response of M. tuberculosis to nutrient starvation. Proteome analysis of 6-week-starved cultures revealed the induction of several proteins. Microarray analysis enabled us to monitor gene expression during adaptation to nutrient starvation and confirmed the changes seen at the protein level. This has provided evidence for slowdown of the transcription apparatus, energy metabolism, lipid biosynthesis and cell division in addition to induction of the stringent response and several other genes that may play a role in maintaining long-term survival within the host. Thus, we have generated a model with which we can search for agents active against persistent M. tuberculosis and revealed a number of potential targets expressed under these conditions.

0 comments Cited 399 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The Danish Civil Registration System. A cohort of eight million persons.

Carsten Bøcker Pedersen, Heine Gøtzsche, Jørgen Ostrup Møller … (2006)

The Danish Civil Registration System (CRS) was established in 1968, where all persons alive and living in Denmark were registered. Among many other variables, it includes individual information on personal identification number, gender, date of birth, place of birth, place of residence, citizenship, continuously updated information on vital status, and the identity of parents and spouses. To evaluate the quality and completeness of the information recorded on persons in the CRS, we considered all persons registered on November 4, 2005, i.e. all persons who were alive and resident in Denmark at least one day from April 2, 1968 to November 4, 2005, or in Greenland from May 1, 1972 to November 4, 2005. A total of 8,176,097 persons were registered. On November 4, 2005, 5,427,687 (66.4%) were alive and resident in Denmark, 56,920 (0.7%) were alive and resident in Greenland, 2,141,373 (26.2%) were dead, 21,160 (0.3%) had disappeared, and 528,957 (6.5%) had emigrated. Among persons born in Denmark 1960 or later the CRS contains complete information on maternal identity. Among persons born in Denmark 1970 or later the CRS contains complete information on paternal identity. Among women born in Denmark April 1935 or later the CRS contains complete information on all their children. Among males born in Denmark April 1945 or later the CRS contains complete information on all their children. The CRS contains complete information on: a) immigrations and emigrations from 1971 onwards, b) permanent residence in a Danish municipality from 1971 onwards, c) permanent residence in a municipality in Greenland from May 1972 onwards, and d) full address in Denmark from 1977 onwards. Data from the CRS is an important research tool in epidemiological research, which enables Danish researchers to carry out representative population-based studies on e.g. the potential clustering of disease and death in families and the potential association between residence and disease and death.

0 comments Cited 365 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Vaccines against Tuberculosis: Where Are We and Where Do We Need to Go?

Tom H. M. Ottenhoff, Stefan Kaufmann (2012)

In this review we discuss recent progress in the development, testing, and clinical evaluation of new vaccines against tuberculosis (TB). Over the last 20 years, tremendous progress has been made in TB vaccine research and development: from a pipeline virtually empty of new TB candidate vaccines in the early 1990s, to an era in which a dozen novel TB vaccine candidates have been and are being evaluated in human clinical trials. In addition, innovative approaches are being pursued to further improve existing vaccines, as well as discover new ones. Thus, there is good reason for optimism in the field of TB vaccines that it will be possible to develop better vaccines than BCG, which is still the only vaccine available against TB.

0 comments Cited 160 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Pere-Joan Cardona: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 1 June 2017

Publication date Collection: 2017

Volume: 12

Issue: 6

Electronic Location Identifier: e0177906

Affiliations

[1 ]Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark

[2 ]Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark

[3 ]Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

[4 ]Department of Medicine, Stanford School of Medicine, Stanford, California, United States of America

Fundació Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, SPAIN

Author notes

Competing Interests: The authors have declared that no competing interests exist.

Conceptualization: SWM BS MM AK STH EMA LJD JW.
Data curation: LJD JW SWM.
Formal analysis: LJD JW SWM BS MM.
Funding acquisition: SWM BS MM.
Investigation: SWM BS STH EMA AK IR.
Methodology: SWM JW BS MM STH EMA LJD AK IR.
Project administration: SWM.
Resources: MM JW AK EMA STH IR SWM.
Software: LJD JW SWM.
Supervision: SWM BS MM EMA STH AK JW.
Visualization: SWM LJD JW BS MM.
Writing – original draft: SWM.
Writing – review & editing: SWM BS LJD EMA STH AK IR JW MM.

* E-mail: swm@ 123456ssi.dk

Author information

Sascha Wilk Michelsen http://orcid.org/0000-0002-6499-8581

Anders Koch http://orcid.org/0000-0001-9205-1048

Jan Wohlfahrt http://orcid.org/0000-0002-0019-2247

Article

Publisher ID: PONE-D-16-49217

DOI: 10.1371/journal.pone.0177906

PMC ID: 5453477

PubMed ID: 28570574

SO-VID: 8a3651cf-2c70-4010-a4f8-3f28cf72123f

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 26 December 2016

Date accepted : 4 May 2017

Page count

Figures: 2, Tables: 5, Pages: 22