Role of trehalose dimycolate in recruitment of cells and modulation of production of cytokines and NO in tuberculosis

Mice treated with viable Mycobacterium tuberculosis with no glycolipid treh alose dimycolate (TDM) on the outer cell wall (delipidated M. tuberculosis) by intraperitoneal or intratracheal inoculation presented an intense recru itment of polymorphonuclear cells into the peritoneal cavity and an acute i nflammatory reaction in the lungs, respectively. In addition, lung lesions were resolved around the 32nd day after intratracheal inoculation. TDM-load ed biodegradable poly-DL-lactide-coglycolide microspheres as well as TDM-co ated charcoal particles induced an intense inflammatory reaction. In additi on, high levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-a lpha), IL-12, IL-10, gamma interferon (IFN-gamma), and IL-4 production were detected in lung cells, and nitric oxide (NO) production was high in cultu re supernatants of bronchoalveolar lavage cells. These in vivo data were co nfirmed by in vitro experiments using peritoneal macrophages cultured in th e presence of TDM adsorbed onto coverslips. High levels of IFN-gamma, IL-6, TNF-alpha, IL-12, IL-10, and NO were detected in the culture supernatants. Our results suggest that TDM contributes to persistence of infection throu gh production of cytokines, which are important for the recruitment of infl ammatory cells and maintenance of a granulomatous reaction. In addition, ou r findings are important for a better understanding of the immunostimulator y activity of TDM and its possible use as an adjuvant in experiments using DNA vaccine or gene therapy against tuberculosis.