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Mycobacterium tuberculosis and the host response.

Kaufmann SH, Cole ST, Mizrahi V, Rubin E, Nathan C - J. Exp. Med. (2005)

Bottom Line: Mycobacterium tuberculosis remains a leading cause of morbidity and mortality worldwide.Advances reported at a recent international meeting highlight insights and controversies in the genetics of M. tuberculosis and the infected host, the nature of protective immune responses, adaptation of the bacillus to host-imposed stresses, animal models, and new techniques.

View Article: PubMed Central - PubMed

Affiliation: Max Plank Institute for Infection Biology, Berlin D10117, Germany.

ABSTRACT
Mycobacterium tuberculosis remains a leading cause of morbidity and mortality worldwide. Advances reported at a recent international meeting highlight insights and controversies in the genetics of M. tuberculosis and the infected host, the nature of protective immune responses, adaptation of the bacillus to host-imposed stresses, animal models, and new techniques.

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Schematic description of the underlying mechanism of improved T cell stimulation by a novel BCG vaccine. Recombinant BCG deleted in urease and expressing listeriolysin is capable of inducing a more profound immune response than wild-type BCG. The likely mechanism involves perforation of the phagosomal membrane, which allows leakage into the cytosol of both mycobacterial antigens and phagosomal enzymes such as cathepsins. Cathepsins are known to induce apoptosis. Thus, the new BCG vaccine strain induces crosspriming leading to a more efficacious immune response. Image provided by Stefan Kaufmann (Berlin, Germany) (25).
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fig2: Schematic description of the underlying mechanism of improved T cell stimulation by a novel BCG vaccine. Recombinant BCG deleted in urease and expressing listeriolysin is capable of inducing a more profound immune response than wild-type BCG. The likely mechanism involves perforation of the phagosomal membrane, which allows leakage into the cytosol of both mycobacterial antigens and phagosomal enzymes such as cathepsins. Cathepsins are known to induce apoptosis. Thus, the new BCG vaccine strain induces crosspriming leading to a more efficacious immune response. Image provided by Stefan Kaufmann (Berlin, Germany) (25).

Mentions: Kaufmann's group engineered recombinant BCG by deleting urease and introducing the L. monocytogenes pore-forming protein listeriolysin to enhance presentation of BCG antigens by MHC class I. The recombinant BCG induced better protection against Mtb in mice than native BCG. Although the emphasis was originally placed on antigen translocation into the cytosol as a route to enhanced recognition of infected host cells by CD8 T cells, this strain has now been found to induce apoptosis of infected host cells, leading to cross presentation (Fig. 2).


Mycobacterium tuberculosis and the host response.

Kaufmann SH, Cole ST, Mizrahi V, Rubin E, Nathan C - J. Exp. Med. (2005)

Schematic description of the underlying mechanism of improved T cell stimulation by a novel BCG vaccine. Recombinant BCG deleted in urease and expressing listeriolysin is capable of inducing a more profound immune response than wild-type BCG. The likely mechanism involves perforation of the phagosomal membrane, which allows leakage into the cytosol of both mycobacterial antigens and phagosomal enzymes such as cathepsins. Cathepsins are known to induce apoptosis. Thus, the new BCG vaccine strain induces crosspriming leading to a more efficacious immune response. Image provided by Stefan Kaufmann (Berlin, Germany) (25).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2213264&req=5

fig2: Schematic description of the underlying mechanism of improved T cell stimulation by a novel BCG vaccine. Recombinant BCG deleted in urease and expressing listeriolysin is capable of inducing a more profound immune response than wild-type BCG. The likely mechanism involves perforation of the phagosomal membrane, which allows leakage into the cytosol of both mycobacterial antigens and phagosomal enzymes such as cathepsins. Cathepsins are known to induce apoptosis. Thus, the new BCG vaccine strain induces crosspriming leading to a more efficacious immune response. Image provided by Stefan Kaufmann (Berlin, Germany) (25).
Mentions: Kaufmann's group engineered recombinant BCG by deleting urease and introducing the L. monocytogenes pore-forming protein listeriolysin to enhance presentation of BCG antigens by MHC class I. The recombinant BCG induced better protection against Mtb in mice than native BCG. Although the emphasis was originally placed on antigen translocation into the cytosol as a route to enhanced recognition of infected host cells by CD8 T cells, this strain has now been found to induce apoptosis of infected host cells, leading to cross presentation (Fig. 2).

Bottom Line: Mycobacterium tuberculosis remains a leading cause of morbidity and mortality worldwide.Advances reported at a recent international meeting highlight insights and controversies in the genetics of M. tuberculosis and the infected host, the nature of protective immune responses, adaptation of the bacillus to host-imposed stresses, animal models, and new techniques.

View Article: PubMed Central - PubMed

Affiliation: Max Plank Institute for Infection Biology, Berlin D10117, Germany.

ABSTRACT
Mycobacterium tuberculosis remains a leading cause of morbidity and mortality worldwide. Advances reported at a recent international meeting highlight insights and controversies in the genetics of M. tuberculosis and the infected host, the nature of protective immune responses, adaptation of the bacillus to host-imposed stresses, animal models, and new techniques.

Show MeSH
Related in: MedlinePlus