Enhanced antimycobacterial response to recombinant Mycobacterium bovis BCGexpressing latency-associated peptide

With a view to exploring the role of transforming growth factor beta (TGF-b eta) during mycobacterial infection, recombinant clones of bacillus Calmett e-Guerin (BCG) were engineered to express the natural antagonist of TGF-bet a, latency-activated peptide (LAP). Induction of TGF-beta activity was redu ced when macrophages were infected with BCG expressing the LAP construct (L AP-BCG). There was a significant reduction in the growth of LAP-BCG in comp arison to that of control BCG following intravenous infection in a mouse mo del. 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, represent ing tissue pathology, were also lower in mice infected with LAP-BCG. The re sults are consistent with the hypothesis that TGF-beta has a detrimental ef fect on mycobacterial immunity. While a reduction in TGF-beta activity augm ents the initial response to BCG vaccination, early bacterial clearance may adversely affect the induction of a long-term memory response by LAP-BCG.