title: Preexisting inflammation due to Mycobacterium bovis BCG infection differentially modulates T-cell priming against a replicating or nonreplicating immunogen.
abstract: Induction of T-cell memory by vaccination ensures long-term protection against pathogens. We determined whether on-going inflammatory responses during vaccination influenced T-cell priming. A preexposure of mice to Mycobacterium bovis BCG impaired their subsequent ability to prime T cells against Listeria monocytogenes. This was characterized by a decrease in L. monocytogenes-specific gamma interferon (IFN-gamma)-secreting CD4(+) and CD8(+) T cells. The intensity of T-cell priming towards L. monocytogenes depended on the extent of L. monocytogenes expansion, and a cessation of this expansion caused by M. bovis BCG-induced inflammation resulted in impairment in T-cell priming. A challenge of M. bovis BCG-infected mice with a higher L. monocytogenes dose increased L. monocytogenes survival and restored T-cell priming towards L. monocytogenes. Impairment in T-cell priming towards L. monocytogenes due to M. bovis BCG-induced inflammation resulted in a compromised protective efficacy in the long term after mice were rechallenged with L. monocytogenes. Preexisting inflammation selectively impaired T-cell priming for replicating immunogens as CD8(+) T-cell response to ovalbumin administered as an inert antigen (ovalbumin-archaeosomes) was enhanced by M. bovis BCG preimmunization, whereas priming towards ovalbumin administered as a live immunogen (L. monocytogenes-ovalbumin) was impaired. Thus, depending on the nature of the immunogen, the presence of prior inflammatory responses may either impede or boost vaccine efficacy.
authors.affiliation: Laboratory of Cellular Immunology, Institute for Biological Sciences, National Research Council, Ottawa, Ontario, Canada.
authors.forename: Renu
authors.initials: R
authors.lastname: Dudani
authors.forename: Yvan
authors.initials: Y
authors.lastname: Chapdelaine
authors.forename: Henk
authors.initials: H
authors.lastname: van Faassen
authors.forename: Dean K
authors.initials: DK
authors.lastname: Smith
authors.forename: Hao
authors.initials: H
authors.lastname: Shen
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Krishnan
authors.forename: Subash
authors.initials: S
authors.lastname: Sad
mesh_terms: D000818:Animals; D001427:Bacterial Toxins; D005260:Female; D006360:Heat-Shock Proteins / Q000276:immunology; D006460:Hemolysin Proteins; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; C038705:hlyA protein, Listeria monocytogenes