Protective immunity to experimental tuberculosis by mannophosphoinositides of mycobacteria

Abstract

Mannophosphoinositides isolated from mycobacterial cells were found to induce both humoral and cell-mediated immune responses in mice when injected as mannoside-methylated bovine serum albumin (MBSA) complexes. Immunization of mice with mannoside-MBSA complexes elicited significant protection against challenge with LDso dose of M. tuberculosis H37Rv as revealed by high survival rate, low values of root-specific lung weight, lung densities and colony forming units recovered from lung, liver and spleen, compared to the nonimmunized group. These observations were further substantiated by histopathological studies. The protective immunity elicited by mannoside-MBSA complexes against challenge with 3/. tuberculosis H37Rv was mediated by the cooperation of T-B ceils, as shown by the passive transfer of immune ceUs/sera' into syngeneic sublethally irradiated recipient mice.

Do CD1-Restricted T Cells Contribute to Antibody-Mediated Immunity againstMycobacterium tuberculosis?

“…Khuller and colleagues demonstrated that the M. tuberculosis glycolipid phosphatidylinositol mannoside (PIM) could induce protective Ab responses in mice immunized with liposome-encapsulated or bovine serum albumin-conjugated vaccines (53,71). Immunization with PIM decreased the bacterial burden in the lungs and prolonged survival.…”

“…Vaccine candidates consisting of LAM-derived oligosaccharides conjugated to protein carriers prolonged survival and prevented weight loss in mice and guinea pigs infected with a virulent strain of M. tuberculosis (32 It is worth highlighting that the effect on CFU was noted early after infection, prior to the development of effective cell-mediated immunity (29). As mentioned, PIM-containing liposomes or PIM-bovine serum albumin conjugates have been used as vaccines to stimulate Ab-mediated protection in mice challenged with M. tuberculosis (53,71). These results provide a strong basis for continued investigation of polysaccharideand glycolipid/lipoglycan-derived vaccines and new investigations into the mechanism(s) of protective Ab production.…”

Activation of mouse peritoneal macrophages by mannophosphoinositides of mycobacteria

“…was maintained on Lowenstein-Jensen or modified Youman's medium [15]. Mannosides were isolated and purified from mycobacterial cells by preparative thin layer chromatography as described in a previous paper [10].…”

“…Recently, we have demonstrated that these components induced protective immunity against experimental tuberculosis [15] when injected as mannoside-methylated bovine serum albumin (MBSA) complexes, a response mediated by the cooperation of T-B cells. Although mice immunized with mannoside-MBSA complexes elicited significant humoral and cell mediated immune (CMI) responses specifically towards mannosides [15], macrophage functions were not investigated.…”

“…Recently, we have demonstrated that these components induced protective immunity against experimental tuberculosis [15] when injected as mannoside-methylated bovine serum albumin (MBSA) complexes, a response mediated by the cooperation of T-B cells. Although mice immunized with mannoside-MBSA complexes elicited significant humoral and cell mediated immune (CMI) responses specifically towards mannosides [15], macrophage functions were not investigated. Because immunologically-activated macrophages are essential for controlling infections with facultative intracellular bacteria [7] such as mycobacteria, the present study was planned to examine the macrophage functions of mannoside-MBSA immunized and unimmunized animals in an in vitro system.…”