title: Liposomal delivery of Mycobacterium leprae antigen(s) with murabutide and Trat peptide inhibits Fas-mediated apoptosis of peripheral blood mononuclear cells derived from leprosy patients.
abstract: Protective immunity against intracellular pathogen Mycobacterium leprae is dependent on the activation of T cells. Repeated stimulation of T cells by M. leprae antigens MLCwA (M. leprae total cell wall antigen) and ManLAM (mannose capped lipoarabinomannan) may lead to apoptosis in leprosy patients. In the present study, inhibition of the Fas-induced apoptosis of peripheral blood mononuclear cells of leprosy patients was investigated using above M. leprae antigen(s), in combination with immunomodulators murabutide (MB) and a Trat peptide in particulate form (liposome). Incubation of the cells with particulate mode of antigen presentation led to both decreased percentage of propidium iodide (PI) positive cells and T cells expressing Fas-FasL, as well as decreased caspase-8/-3 activities in the lepromatous patients, thereby inhibiting apoptosis, while converse was true with stimulation with soluble antigen. Concurrently, there was an upregulation of antiapoptotic protein Bcl-X(L) in the lepromatous patients, thereby inhibiting apoptosis. Thus, the liposomal formulation of antigen promoted proliferation of anergized T cell by inhibiting apoptosis through decreased expression of death receptors and caspase activities and increased expression of anti-apoptotic protein Bcl-X(L) in these patients.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029.
authors.forename: Vineeta
authors.initials: V
authors.lastname: Chattree
authors.forename: Neena
authors.initials: N
authors.lastname: Khanna
authors.forename: Vandana
authors.initials: V
authors.lastname: Bisht
authors.forename: D N
authors.initials: DN
authors.lastname: Rao
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage*; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods; D029968:Escherichia coli Proteins / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007918:Leprosy / Q000276:immunology* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology*; D008081:Liposomes / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D019014:fas Receptor / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D008081:Liposomes; C036297:TraT protein, E coli; D019014:fas Receptor; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C033575:murabutide