1887

Abstract

Three proteins, PE_PGRS 16 (Rv0977), PE_PGRS 26 (Rv1441c) and PE_PGRS 33 (Rv1818c), were expressed in and used to investigate the host response to members of this unique protein family. Following infection of macrophages with the recombinant () strains, -PE_PGRS 33 and -PE_PGRS 26 were significantly more persistent (4.4 and 4.2 log c.f.u.) compared with -PE_PGRS 16 (3.4 log c.f.u.) at day 6. Similarly, after infection of mice, -PE_PGRS 33 and -PE_PGRS 26 persisted at significantly higher levels in the spleen (3.5 and 3.2 log c.f.u.) and liver (3 and 2.6 log c.f.u.) compared with -PE_PGRS 16 in the spleen (2 log c.f.u.) and in the liver (1 log c.f.u.) at day 10. Increased persistence of -PE_PGRS 33 and -PE_PGRS 26 was associated with cell death and increased release of lactate dehydrogenase in macrophage cultures as well as increased levels of IL-10 and, in contrast, lower levels of IL-12 and NO both and in mouse splenocytes. Conversely, poor survival of -PE_PGRS 16 was associated both in macrophage cultures and with higher levels of NO and IL-12. All three PE_PGRS proteins were found to be cell-surface antigens, but immunization of mice with these PE_PGRS antigens as DNA vaccines showed no protection in a TB aerosol challenge model. In general, the results suggest that variable expression of different PE_PGRS proteins within host cells can affect either the fate of the mycobacterial pathogen or that of the host during infection and point to the importance of studying the expression and function of individual members of the PE_PGRS gene family of .

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2008-11-01
2019-11-20
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Primers and probes used [ PDF] (51 kb) Immunoblot showing expression of PE_PGRS proteins in recombinant strains. Extracts of expressing PE_PGRS 33 (lane 1), PE_PGRS 16 (lane 2) and PE_PGRS 26 (lane 3) were detected with anti-PE_PGRS monoclonal antibody 7C4.IF7 as described in Methods to confirm the expression of these proteins by the strains. [ PDF] (17 kb)

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Primers and probes used [ PDF] (51 kb) Immunoblot showing expression of PE_PGRS proteins in recombinant strains. Extracts of expressing PE_PGRS 33 (lane 1), PE_PGRS 16 (lane 2) and PE_PGRS 26 (lane 3) were detected with anti-PE_PGRS monoclonal antibody 7C4.IF7 as described in Methods to confirm the expression of these proteins by the strains. [ PDF] (17 kb)

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