Lung hydrolases modify the course of Mycobacterium tuberculosis infection in vivo (MPF3P.806)

Mycobacterium tuberculosis ( M.tb ) kills one person every 18 seconds. Upon M.tb deposition in the airways, bacilli are bathed in alveolar lining fluid (ALF). Our published data indicate that hydrolytic enzymes present in ALF modify the cell wall of M.tb with two outcomes: cell wall modifications and release of cell wall fragments into the milieu. These modifications resulted in an altered macrophage immune response in vitro . Here we used the low dose aerosol mouse model of M.tb infection to assess if ALF/hydrolase-derived modifications of M.tb alter the immune response to infection in vivo . Our current data indicate that ALF/hydrolase-derived modifications on the M.tb cell wall led to increased CD4 and CD8 T cell numbers and activation in the lung, and altered cytokine secretion (increased TNF, IL-12 and IFN-γ), important for control of M.tb infection. These results correlated with an improvement of the M.tb burden within the lung starting on day 21 of infection. Thus, our results support the concept of human ALF hydrolases being novel immune components that can influence the generation of immune responses during M.tb infection.