Regulation von antimikrobiellen Peptiden bei der Tuberkulose
Hagemann, Jürgen Benjamin
The main issue of this experimental work was to investigate the regulation of antimicrobial peptides in tuberculosis with a special focus on T-cell clones (characterized as CD4+, TZR alpha ß+, CD1-restricted and specifically activated by mycobacterial lipid antigens), macrophages (M Phi) and peripheral blood mononuclear cells (PBMC). The expression of a selective panel of immunologically important molecules was analyzed using quantitative real time PCR (qRT-PCR), the enzyme linked immunosorbent assay (ELISA) as well as flow cytometry. After stimulation with mycobacterial lipid antigens, we measured the regulation of cathepsin G (CathG), cathelicidin, toll-like receptor 2 (TLR-2) and purinoceptor P2X7 in M Phi on the one hand as well as the expression of gamma-interferon (IFN gamma), perforin and granulysin in T-cell clones on the other hand. The results found were then transferred to primary human cells (monocytes and T-lymphocytes) generated from PBMC. We found that stimulation with mycobacterial antigens leads to a significant up-regulation of TLR-2 and P2X7 in M Phi as well as to an increase of the transcription and secretion of IFN gamma in T-cell clones. The latter also expressed more granulysin - a result likewise reproducible in primary human T-lymphocytes of PPD+ donors, especially in the CD4+ subpopulation. Our data therefore support a theory assuming mycobacterial lipids to have an enormous potential as regards manipulating and inducing protective immunity. Selective application of mycobacterial lipid antigens in the context of preventive strategies and vaccination might stimulate protective T-cell populations expressing granulysin, enabling them to avoid active tuberculosis. The data collected suggest using lipids as possible vaccination antigens or as immunomodulatory molecules in a targeted therapy of tuberculosis.
Subject HeadingsAntigen CD4 [GND]
Enzyme-linked immunosorbent assay [GND]
Enzyme linked immunosorbent assay [MeSH]