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

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          Summary

          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.

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          Most cited references48

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          IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge.

          Interferon-gamma is key in limiting Mycobacterium tuberculosis infection. Here we show that vaccination triggered an accelerated interferon-gamma response by CD4(+) T cells in the lung during subsequent M. tuberculosis infection. Interleukin 23 (IL-23) was essential for the accelerated response, for early cessation of bacterial growth and for establishment of an IL-17-producing CD4(+) T cell population in the lung. The recall response of the IL-17-producing CD4(+) T cell population occurred concurrently with expression of the chemokines CXCL9, CXCL10 and CXCL11. Depletion of IL-17 during challenge reduced the chemokine expression and accumulation of CD4(+) T cells producing interferon-gamma in the lung. We propose that vaccination induces IL-17-producing CD4(+) T cells that populate the lung and, after challenge, trigger the production of chemokines that recruit CD4(+) T cells producing interferon-gamma, which ultimately restrict bacterial growth.
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            Variation in protection by BCG: implications of and for heterologous immunity.

            P E Fine (1995)
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              Failure of the Mycobacterium bovis BCG vaccine: some species of environmental mycobacteria block multiplication of BCG and induction of protective immunity to tuberculosis.

              The efficacy of Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine against pulmonary tuberculosis (TB) varies enormously in different populations. The prevailing hypothesis attributes this variation to interactions between the vaccine and mycobacteria common in the environment, but the precise mechanism has so far not been clarified. Our study demonstrates that prior exposure to live environmental mycobacteria can result in a broad immune response that is recalled rapidly after BCG vaccination and controls the multiplication of the vaccine. In these sensitized mice, BCG elicits only a transient immune response with a low frequency of mycobacterium-specific cells and no protective immunity against TB. In contrast, the efficacy of TB subunit vaccines was unaffected by prior exposure to environmental mycobacteria. Six different isolates from soil and sputum samples from Karonga district in Northern Malawi (a region in which BCG vaccination has no effect against pulmonary TB) were investigated in the mouse model, and two strains of the Mycobacterium avium complex were found to block BCG activity completely.
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                Author and article information

                Contributors
                Journal
                Tuberculosis (Edinb)
                Tuberculosis (Edinb)
                Tuberculosis (Edinburgh, Scotland)
                Churchill Livingstone
                1472-9792
                1873-281X
                1 May 2014
                May 2014
                : 94
                : 3
                : 226-237
                Affiliations
                [1]The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom
                Author notes
                []Corresponding author. Present address: Malaghan Institute of Medical Research, PO Box 7060, Wellington 6242, New Zealand. Tel.: +64 4 499 6914; fax: +64 4 499 6915. hpoyntz@ 123456malaghan.org.nz
                [1]

                Present address: Research School of Biology, Australian National University, Canberra ACT 0200, Australia.

                [2]

                Present address: London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, United Kingdom.

                Article
                S1472-9792(13)00224-2
                10.1016/j.tube.2013.12.006
                4066954
                24572168
                f4d789e8-ceda-4564-bf6f-5bb110b44183
                © 2014 The Authors
                History
                : 15 August 2013
                : 30 November 2013
                : 23 December 2013
                Categories
                Immunological Aspects

                Respiratory medicine
                bacillus calmette-geurin,non-tuberculous mycobacteria,mycobacterium avium,tuberculosis,mouse model

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