Influence of serum on the immune recognition of a synthetic lipopeptide mimetic of the 19-kDa lipoprotein from Mycobacterium tuberculosis.
The innate immune response provides a critical first-line defense against Mycobacterium tuberculosis, an intracellular pathogen that represents a major health threat world-wide. A synthetic lipopeptide (LP) mimicking the lipid moiety of the cell-wall associated 19-kDa lipoprotein from M. tuberculosis has recently been assigned an important role in the induction of an antibacterial immune response in host macrophages. Here, we present experimental data on the biological activities and the biophysical mechanisms underlying cell activation by synthetic 19-kDa M. tuberculosis-derived lipopeptide (Mtb-LP). Investigation of the geometry of the LP (i.e. the molecular conformation and supramolecular aggregate structure) and the preference for membrane intercalation provide an explanation for the biological activities of the mycobacterial LP. Cell activation by low concentrations of Mtb-LP was enhanced by the lipopolysaccharide-binding protein and CD14. However, surprisingly, we found that activation of human macrophages to induce pro- as well as antiinflammatory mediators (tumor necrosis factor(TNF)-alpha, Interleukin(IL)-6, IL-8, and IL-10) in response to the Mtb-LP is strongly reduced in the presence of serum. This observation could be confirmed for the immune response of murine macrophages which showed a strongly enhanced TNF-alpha release in the absence of serum, suggesting that the molecular mechanisms of immune recognition of the Mtb-LP are tailored to the ambient conditions of the lung.
Schromm
Andra B
AB
Department of Molecular Infection Biology, Emmy Noether Group of Immunobiophysics, Leibniz-Center for Medicine and Biosciences, Research Center Borstel, Borstel, Germany. aschromm@fz-borstel.de
Reiling
Norbert
N
Howe
Jörg
J
Wiesmüller
Karl-Heinz
KH
Roessle
Manfred
M
Brandenburg
Klaus
K
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D032701:Biomimetics; D001854:Bone Marrow Cells / Q000276:immunology; D016895:Culture Media, Serum-Free; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D007202:Indicators and Reagents; D007249:Inflammation / Q000276:immunology; D008055:Lipids / Q000737:chemistry; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000276:immunology*; D044967:Serum / Q000276:immunology*; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
C087864:19 kDa antigen, Mycobacterium; D001426:Bacterial Proteins; D016895:Culture Media, Serum-Free; D016207:Cytokines; D007202:Indicators and Reagents; D008055:Lipids