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Broad adaptive immune responses to M. tuberculosis antigens precede TST conversion in tuberculosis exposed household contacts in a TB-endemic setting.
- Source :
-
PloS one [PLoS One] 2014 Dec 30; Vol. 9 (12), pp. e116268. Date of Electronic Publication: 2014 Dec 30 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- Background: The identification of Mycobacterium-tuberculosis (Mtb) infected individuals remains a challenge due to an insufficient understanding of immune responses detected with the current diagnostic tests for latent tuberculosis i.e. the tuberculin skin test (TST) or IFN-γ release assays (IGRAs) and an inability to distinguish infection stages with current immunologic assays. Further classification based on markers other than IFN-γ may help to define markers of early Mtb infection.<br />Methods: We assessed the TST status of Mtb-exposed household contacts at baseline and at 6 months. Contacts were classified into those with initial positive TST (TST+); those with baseline negative TST but TST conversion at 6 months (TST converters, TSTC) and those with persistently negative TST (PTST-). We assessed their short- and long-term immune responses to PPD and ESAT-6/CFP-10 (EC) via IFN-γ ELISPOT and a multiplex cytokine array in relation to TST status and compared them to those of TB cases to identify immune profiles associated with a spectrum of infection stages.<br />Results: After 1 and 6 days stimulation with EC, 12 cytokines (IFN-γ, IL-2, IP-10, TNF-α, IL-13, IL-17, IL-10, GMCSF, MIP-1β, MCP-3, IL-2RA and IL-1A) were not different in TSTC compared to TST+ suggesting that robust adaptive Mtb-specific immune responses precede TST conversion. Stratifying contacts by baseline IFN-γ ELISPOT to EC in combination with TST results revealed that IP-10 and IL-17 were highest in the group of TST converters with positive baseline ELISPOT, suggesting they might be markers for recent infection.<br />Conclusion: We describe a detailed analysis of Mtb-specific biomarker profiles in exposed household contacts in a TB endemic area that provides insights into the dynamic immune responses to Mtb infection and may help to identify biomarkers for 'at-risk' populations beyond TST and IGRA.
- Subjects :
- Adult
Cells, Cultured
Endemic Diseases
Female
Humans
Male
Middle Aged
Mycobacterium tuberculosis immunology
Tuberculin Test
Tuberculosis immunology
Tuberculosis metabolism
Young Adult
Antigens, Bacterial immunology
Contact Tracing
Interferon-gamma metabolism
Mycobacterium tuberculosis isolation & purification
Tuberculosis diagnosis
Tuberculosis epidemiology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 25549338
- Full Text :
- https://doi.org/10.1371/journal.pone.0116268