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Tuberculosis (Edinb). 2014 May;94(3):226-37. doi: 10.1016/j.tube.2013.12.006. Epub 2014 Jan 2.

Non-tuberculous mycobacteria have diverse effects on BCG efficacy against Mycobacterium tuberculosis.

Author information

1
The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom. Electronic address: hpoyntz@malaghan.org.nz.
2
The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom. Electronic address: elena.stylianou@ndm.ox.ac.uk.
3
The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom. Electronic address: Kristin.griffiths@gmail.com.
4
The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom. Electronic address: Leanne.marsay@ndm.ox.ac.uk.
5
The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom. Electronic address: annacheckley@yahoo.com.
6
The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom. Electronic address: Helen.mcshane@ndm.ox.ac.uk.

Abstract

The efficacy of Bacillus Calmette-Guerin (BCG) vaccination in protection against pulmonary tuberculosis (TB) is highly variable between populations. One possible explanation for this variability is increased exposure of certain populations to non-tuberculous mycobacteria (NTM). This study used a murine model to determine the effect that exposure to NTM after BCG vaccination had on the efficacy of BCG against aerosol Mycobacterium tuberculosis challenge. The effects of administering live Mycobacterium avium (MA) by an oral route and killed MA by a systemic route on BCG-induced protection were evaluated. CD4+ and CD8+ T cell responses were profiled to define the immunological mechanisms underlying any effect on BCG efficacy. BCG efficacy was enhanced by exposure to killed MA administered by a systemic route; T helper 1 and T helper 17 responses were associated with increased protection. BCG efficacy was reduced by exposure to live MA administered by the oral route; T helper 2 cells were associated with reduced protection. These findings demonstrate that exposure to NTM can induce opposite effects on BCG efficacy depending on route of exposure and viability of NTM. A reproducible model of NTM exposure would be valuable in the evaluation of novel TB vaccine candidates.

KEYWORDS:

Bacillus Calmette-Geurin; Mouse model; Mycobacterium avium; Non-tuberculous mycobacteria; Tuberculosis

PMID:
24572168
PMCID:
PMC4066954
DOI:
10.1016/j.tube.2013.12.006
[Indexed for MEDLINE]
Free PMC Article

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