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Infection and Immunity, November 2001, p. 6676-6682, Vol. 69, No. 11
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.11.6676-6682.2001

Enhanced Antimycobacterial Response to Recombinant Mycobacterium bovis BCG Expressing Latency-Associated Peptide

Ben G. Marshall,1,2,* Arun Wangoo,1 Peadar O'Gaora,2 H. Terry Cook,3 Rory J. Shaw,1 and Douglas B. Young2

Department of Respiratory Medicine, National Heart and Lung Institute,1 and Departments of Pathology3 and Infectious Diseases and Microbiology,2 Imperial College School of Medicine, London, United Kingdom

Received 2 April 2001/Returned for modification 24 May 2001/Accepted 26 July 2001

With a view to exploring the role of transforming growth factor beta  (TGF-beta ) during mycobacterial infection, recombinant clones of bacillus Calmette-Guérin (BCG) were engineered to express the natural antagonist of TGF-beta , latency-activated peptide (LAP). Induction of TGF-beta activity was reduced when macrophages were infected with BCG expressing the LAP construct (LAP-BCG). There was a significant reduction in the growth of LAP-BCG in comparison to that of control BCG following intravenous infection in a mouse model. The enhanced control of mycobacterial replication was associated with an increase in the production of gamma interferon by splenocytes challenged during the acute stage of infection but with a diminished recall response assessed after 13 weeks. Organ weight and hydroxyproline content, representing tissue pathology, were also lower in mice infected with LAP-BCG. The results are consistent with the hypothesis that TGF-beta has a detrimental effect on mycobacterial immunity. While a reduction in TGF-beta activity augments the initial response to BCG vaccination, early bacterial clearance may adversely affect the induction of a long-term memory response by LAP-BCG.

* Corresponding author. Mailing address: Department of Respiratory Medicine, Southampton University Hospitals NHS Trust, Southampton, Hampshire, United Kingdom. Phone: 44 2380 796228. Fax: 44 2380 794585. E-mail:ben.marshall{at}suht.swest.nhs.uk.

Infection and Immunity, November 2001, p. 6676-6682, Vol. 69, No. 11
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.11.6676-6682.2001


This article has been cited by other articles:

  • Weiss, D. J., Evanson, O. A., Deng, M., Abrahamsen, M. S. (2004). Gene Expression and Antimicrobial Activity of Bovine Macrophages in Response to Mycobacterium avium subsp. paratuberculosis. Veterinary Pathology 41: 326-337 [Abstract] [Full Text]  
  • Young, D. B, Stewart, G. R (2002). Tuberculosis vaccines. Br Med Bull 62: 73-86 [Abstract] [Full Text]  


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