Antibodies have demonstrated having a protective effect in animal models of tuberculosis (TB). These experiments have considered the specificity of antigen recognition and the different isotypes and subclasses as significant contributors of this effect. However, the carbohydrate chain heterogeneity on the Fc region of IgG (Fc-IgG) can play an important role in modulating the immune response. Patients with TB usually have high titers of specific IgG; however, the carbohydrate associated with Fc-IgG usually lacks galactose. To assess the effect of this abnormal IgG in murine pulmonary TB, we evaluated the specificity of recognition to Mycobacterium tuberculosis antigens in vitro and protective effects in vivo comparing human intravenous immunoglobulin (IVIg) and IVIg treated with an endoglycosidase to remove the glycan residues (EndoS-treated IVIg). Our results showed similar antigen recognition. The study of distribution and kinetics of IVIg in serum and bronchial lavage after intraperitoneal (i.p.) administration in mice showed that IVIg circulates for 21 days. Finally, the protective effect of intact and EndoS-treated IVIg administered by i.p was studied in a murine model of progressive TB. IVIg treatment caused reduction in pulmonary bacilli loads, larger granulomas, and less pneumonia, while animals treated with EndoS-treated IVIg were not protected compared with control animals. Thus, IVIg has a protective activity in experimental pulmonary TB, and this effect requires intact Fc oligosaccharides.
Caulerpin (1a), a bis-indole alkaloid from the marine algal Caulerpa sp., was synthesized in three reaction steps with an overall yield of 11%. The caulerpin analogues (1b–1g) were prepared using the same synthetic pathway with overall yields between 3% and 8%. The key reaction involved a radical oxidative aromatic substitution involving xanthate (3) and 3-formylindole compounds (4a–4g). All bis-indole compounds synthesized were evaluated against the Mycobacterium tuberculosis strain H37Rv, and 1a was found to display excellent activity (IC50 0.24 µM).
Nitro-substituted heteroaromatic carboxamides 1a-e were synthesized and tested against three Mycobacterium tuberculosis cell lines. The activities can be explained in terms of the distribution of the electronic density across the nitro-substituted heteroaromatic ring attached to the amide group. 1,3,5-Oxadiazole derivatives 1c-e are candidates for the development of novel antitubercular agents. Ongoing studies are focused on exploring the mechanism by which these compounds inhibit M. tuberculosis cell growth.
Species of the genus Mycobacterium are capable of inducing cell apoptosis. Infected cells with M. tuberculosis undergo apoptosis through a caspase-dependent pathway. We have previously shown that whole Mycobacterium bovis cells and derived crude protein extracts were able to trigger apoptosis through a caspase independent mechanism. However, the identity of the protein or protein fractions capable of inducing apoptosis has not been determined. In this study, bovine macrophages were incubated in the presence of Mycobacterium tuberculosis recombinant proteins and Mycobacterium bovis protein extracts to identify proteins capable of inducing apoptosis. A subgroup of proteins and protein extracts from strains of the Mycobacterium tuberculosis complex were shown to induce DNA fragmentation in bovine macrophages through a caspase independent pathway. Our findings suggest that bovine macrophages may elicit a different response to mycobacterium infection than that displayed by murine or human cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.