Harnessing the immunostimulatory properties of bacterial ghosts to fight tuberculosis

Tuberculosis (TB) drug resistance has outpaced the development of novel drugs with new modes of action, generating renewed interest in alternative therapeutic approaches capable of improving protective host immune responses. In this context, we investigated the immunomodulatory properties of bacterial ghosts (BG), which are intact Escherichia coli cell envelopes. BG were found to be potent activators of macrophages and dendritic cells (DC), which enhanced production of nitric oxide and T cell proliferation and differentiation, respectively. The immunostimulatory capability of BG far exceeded that of LPS and involved both TLR4-dependent and independent pathways. Furthermore, BG treatment of mice infected with M. bovis BCG or M. tuberculosis significantly reduced the lung bacterial loads. This correlated with greater pulmonary recruitment of myeloid populations involved in mycobacteria clearance, elevated levels of migratory DC and activated CD4+ T cells, and increased production of key cytokines. Overall, our findings support BG as potent immunostimulator that could be harnessed to improve bacterial killing at the site of infection.