Spiralin, a mycoplasmal membrane lipoprotein, induces T-cell-independent B-cell blastogenesis and secretion of proinflammatory cytokines.
Mycoplasmas are bacteria which can cause respiratory, arthritic, and urogenital diseases. During the early phase of infection, mycoplasmas usually induce an inflammatory response and a humoral response preferentially directed against their membrane-bound, surface-exposed lipoproteins. In this report, we describe the effects on immune cells of spiralin, a well-characterized mycoplasmal lipoprotein. Purified spiralin stimulated the in vitro proliferation of human peripheral blood mononuclear cells and murine splenocytes. The stimulation pathway was probably different from that followed by Escherichia coli lipopolysaccharide because the effect of spiralin was not abolished by polymyxin B. Comparison of the effects of whole, native spiralin with those induced by proteinase K-digested spiralin or by the C-terminal half of spiralin (peptide p[13.5]T) revealed that the first half of the protein, which contains the lipoylated N terminus, is responsible for the mitogenic activity. In contrast to whole spiralin, proteinase K-digested spiralin did not trigger murine B-cell differentiation and immunoglobulin G and M secretion. Stimulation of human or murine immune cells led to early secretion of proinflammatory cytokines (human tumor necrosis factor alpha and murine interleukin 1 or 6). Spiralin induced the T-cell-independent blastogenesis of murine B cells but did not stimulate T cells. Altogether, our data demonstrate that spiralin possesses potent immunostimulating activity, similar to that reported for lipoproteins of pathogenic gracilicutes (gram-negative eubacteria; e.g., Borrelia burgdorferi OspA and E. coli Braun lipoprotein), and are consistent with the fact that lipoproteins are major antigens during mycoplasma infections.
Brenner
C
C
Département SIDA et Rétrovirus, Unité d'Oncologie Virale, Institut Pasteur, Paris, France.
Wróblewski
H
H
Le Henaff
M
M
Montagnier
L
L
Blanchard
A
A
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007249:Inflammation / Q000276:immunology; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008074:Lipoproteins / Q000737:chemistry / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D017421:Sequence Analysis; D013149:Spiroplasma / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001425:Bacterial Outer Membrane Proteins; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007375:Interleukin-1; D015850:Interleukin-6; D008074:Lipoproteins; D014409:Tumor Necrosis Factor-alpha; C028588:spiralin