title: Immunotherapeutic potential of N-formylated peptides of ESAT-6 and glutamine synthetase in experimental tuberculosis.
abstract: Recent understanding of the pathogenesis of tuberculosis allows the possible application of immunotherapy for the treatment of tuberculosis. Therapies that would upregulate the host anti mycobacterial innate and/or adaptive immune response have been supposed to be useful in the treatment of tuberculosis. Since N-formyl peptides are products of bacterial metabolism, and their binding to a specific phagocyte receptor (FPR) induces chemotaxis and activation of phagocytes that are critical effectors in our innate immune system, it is reasonable to assume that the interaction between these two counterparts (i.e. formylated peptides and FPR) is also important in host defence against M. tuberculosis. In the present study the direct immunotherapeutic potential of N-formylated peptides of two non-classically secreted proteins (early secreted antigenic target-6 and glutamine synthetase) of M. tuberculosis H37Rv was evaluated. Treatment of M. tuberculosis H37Rv infected mice with N-formylated peptides of early secreted antigenic target-6 (ESAT-6) and glutamine synthetase (GS) markedly reduced the bacilli load in their lungs (p < 0.001) and spleen (p < 0.01) as compared to the untreated mice. In addition, the histopathological changes were observed to be in correlation with the CFU data with minor areas of consolidation in the lung sections of N-formylated peptide treated infected mice as compared to those of the untreated mice. Further, these N-formylated peptides were able to confer an additional therapeutic effect when given in combination with the anti tuberculosis drugs and hence can be used as an adjunct to the conventional chemotherapy against tuberculosis.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh -160012 India.
authors.forename: Shabir Ahmad
authors.initials: SA
authors.lastname: Mir
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh -160012 India. Electronic address: sadhnabiochem@gmail.com.
authors.forename: Sadhna
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000276:immunology*; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000382:microbiology; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007155:Immunologic Factors; D009842:Oligopeptides; D017382:Reactive Oxygen Species; D005974:Glutamate-Ammonia Ligase
keywords: Antituberculosis drugs; Chemotherapy; Early secreted antigenic target-6 and glutamine synthetase; Immunotherapy; N-formylated peptides