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Infection and Immunity, January 2008, p. 351-360, Vol. 76, No. 1
0019-9567/08/$08.00+0     doi:10.1128/IAI.00614-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Bystander Macrophage Apoptosis after Mycobacterium tuberculosis H37Ra Infection{triangledown}

Deirdre M. Kelly, Annemieke M. C. ten Bokum,{dagger} Seonadh M. O'Leary, Mary P. O'Sullivan, and Joseph Keane*

Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, and St. James's Hospital, Dublin, Ireland

Received 1 May 2007/ Returned for modification 19 June 2007/ Accepted 10 October 2007

Human macrophages infected with Mycobacterium tuberculosis may undergo apoptosis. Macrophage apoptosis contributes to the innate immune response against M. tuberculosis by containing and limiting the growth of mycobacteria and also by depriving the bacillus of its niche cell. Apoptosis of infected macrophages is well documented; however, bystander apoptosis of uninfected macrophages has not been described in the setting of M. tuberculosis. We observed that uninfected human macrophages underwent significant bystander apoptosis 48 and 96 h after they came into contact with macrophages infected with avirulent M. tuberculosis. The bystander apoptosis was significantly greater than the background apoptosis observed in uninfected control cells cultured for the same length of time. There was no evidence of the involvement of tumor necrosis factor alpha, Fas, tumor necrosis factor-related apoptosis-inducing ligand, transforming growth factor β, Toll-like receptor 2, or MyD88 in contact-mediated bystander apoptosis. This newly described phenomenon may further limit the spread of M. tuberculosis by eliminating the niche cells on which the bacillus relies.


* Corresponding author. Mailing address: St. James's Hospital, CResT, Dublin 8, Ireland. Phone: 353 1 4103920. Fax: 353 1 4103549. E-mail: jkeane{at}stjames.ie

{triangledown} Published ahead of print on 22 October 2007.

Editor: J. L. Flynn

{dagger} Present address: Department of Infectious & Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.


Infection and Immunity, January 2008, p. 351-360, Vol. 76, No. 1
0019-9567/08/$08.00+0     doi:10.1128/IAI.00614-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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