| Autor: |
Moliva JI; Department Microbial Infection and Immunity, College of Medicine (COM), The Ohio State University (OSU), Columbus, Ohio, USA.; Biomedical Sciences Graduate Program, COM, OSU, Columbus, Ohio, USA., Hossfeld AP; Department Microbial Infection and Immunity, College of Medicine (COM), The Ohio State University (OSU), Columbus, Ohio, USA., Canan CH; Department Microbial Infection and Immunity, College of Medicine (COM), The Ohio State University (OSU), Columbus, Ohio, USA., Dwivedi V; Department Microbial Infection and Immunity, College of Medicine (COM), The Ohio State University (OSU), Columbus, Ohio, USA., Wewers MD; Department Internal Medicine, Pulmonary, Critical Care and Sleep Medicine Division, COM, OSU, Columbus, Ohio, USA., Beamer G; Department Infectious Diseases and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachussetts, USA., Turner J; Department Microbial Infection and Immunity, College of Medicine (COM), The Ohio State University (OSU), Columbus, Ohio, USA., Torrelles JB; Department Microbial Infection and Immunity, College of Medicine (COM), The Ohio State University (OSU), Columbus, Ohio, USA. |
| Abstrakt: |
Current tuberculosis (TB) treatments include chemotherapy and preventative vaccination with Mycobacterium bovis Bacillus Calmette-Guérin (BCG). In humans, however, BCG vaccination fails to fully protect against pulmonary TB. Few studies have considered the impact of the human lung mucosa (alveolar lining fluid (ALF)), which modifies the Mycobacterium tuberculosis (M.tb) cell wall, revealing alternate antigenic epitopes on the bacterium surface that alter its pathogenicity. We hypothesized that ALF-induced modification of BCG would induce better protection against aerosol infection with M.tb. Here we vaccinated mice with ALF-exposed BCG, mimicking the mycobacterial cell surface properties that would be present in the lung during M.tb infection. ALF-exposed BCG-vaccinated mice were more effective at reducing M.tb bacterial burden in the lung and spleen, and had reduced lung inflammation at late stages of M.tb infection. Improved BCG efficacy was associated with increased numbers of memory CD8 + T cells, and CD8 + T cells with the potential to produce interferon-γ in the lung in response to M.tb challenge. Depletion studies confirmed an essential role for CD8 + T cells in controlling M.tb bacterial burden. We conclude that ALF modifications to the M.tb cell wall in vivo are relevant in the context of vaccine design. |
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