The PPE protein family of Mycobacterium tuberculosis includes 69 glycine-rich proteins with a conserved N-terminal domain. Their role in tuberculosis is unknown, but it has been speculated that they may have an important immunological significance. In this investigation, we evaluated the immunogenicity of ppe44 (Rv2770c) gene product in BALB/c mice infected subcutaneously or intravenously with Mycobacterium bovis BCG. Mice infected subcutaneously developed high titers of anti-PPE44 IgG1 antibodies while PPE44-specific IgG2a antibodies were absent at all tested times; PPE44-primed cells from draining lymph nodes and spleen produced low levels of IFN- and a moderate degree of delayed type hypersensitivity was observed following PPE44 intracutaneous challenge. In mice infected intravenously, anti-PPE44 IgG1 antibody response was markedly higher compared to the subcutaneous infection; anti-PPE44 IgG2a antibodies at titers approximately 0.5-2.0 log10 lower than IgG1 were detected. IFN- production in PPE44-stimulated spleen cell cultures was transient. Our results indicate that PPE44 represents a novel mycobacterial antigen expressed during subcutaneous and intravenous infection by M. bovis BCG in BALB/c mice. Both infection models seem to polarize the immune response to PPE44 towards a Th2 phenotype, as testified by the IgG1 isotype predominant over the IgG2a, and by the low IFN-gamma and delayed type hypersensitivity responses.
Immunogenicity of mycobacterial PPE44 (Rv2770c) in Mycobacterium bovis BCG-infected mice
RINDI, LAURA;GARZELLI, CARLO;
2005-01-01
Abstract
The PPE protein family of Mycobacterium tuberculosis includes 69 glycine-rich proteins with a conserved N-terminal domain. Their role in tuberculosis is unknown, but it has been speculated that they may have an important immunological significance. In this investigation, we evaluated the immunogenicity of ppe44 (Rv2770c) gene product in BALB/c mice infected subcutaneously or intravenously with Mycobacterium bovis BCG. Mice infected subcutaneously developed high titers of anti-PPE44 IgG1 antibodies while PPE44-specific IgG2a antibodies were absent at all tested times; PPE44-primed cells from draining lymph nodes and spleen produced low levels of IFN- and a moderate degree of delayed type hypersensitivity was observed following PPE44 intracutaneous challenge. In mice infected intravenously, anti-PPE44 IgG1 antibody response was markedly higher compared to the subcutaneous infection; anti-PPE44 IgG2a antibodies at titers approximately 0.5-2.0 log10 lower than IgG1 were detected. IFN- production in PPE44-stimulated spleen cell cultures was transient. Our results indicate that PPE44 represents a novel mycobacterial antigen expressed during subcutaneous and intravenous infection by M. bovis BCG in BALB/c mice. Both infection models seem to polarize the immune response to PPE44 towards a Th2 phenotype, as testified by the IgG1 isotype predominant over the IgG2a, and by the low IFN-gamma and delayed type hypersensitivity responses.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
