Effects of Mycoplasma fermentans on the myelomonocytic lineage. Different molecular entities with cytokine-inducing and cytocidal potential.
Mycoplasma fermentans is a mycoplasma species that has been accused of serving as a cofactor of AIDS development. Here, we show that M. fermentans affects the function of human monocytes and myelomonocytic cell lines on at least two different levels. Heat-inactivated mycoplasma particles induce inflammatory cytokines such as IL-1, IL-6, and TNF in monocytes, as well as in THP-1 cells. Moreover, M. fermentans induces IL-10 (but not IL-12) in freshly isolated human monocytes. The cytokine-inducing effect is mediated by lipid-associated molecules. In addition, we have detected a novel biologic activity that resides in the nonlipid-associated protein fraction of M. fermentans (approximate molecular mass: 15 to 30 kDa) and that has a cytocidal effect on nondifferentiated myelomonocytic cell lines (U937 cells, HL-60 cells), as well as on actinomycin-D-sensitized monocytes. Death is accompanied by oligonucleosomal DNA fragmentation and loss of chromosomal DNA. U937 and HL-60 cells fail to produce cytokines and rather undergo cell death in response to heat-inactivated M. fermentans, provided that they are kept in a relatively undifferentiated stage. Whereas the cytokine-inducing activity is a general feature of many mycoplasma species, it appears that only a restricted panel of mycoplasma species exert a cell death-inducing activity. In addition to M. fermentans strains, Mycoplasma penetrans, another hypothetical cofactor of AIDS, possess a cytocidal activity. This does not apply to other mycoplasma species, including pathogenic ones such as Mycoplasma pneumoniae and Ureaplasma urealyticum. The cell death-inducing effect of M. fermentans is not mediated by cytokines and obeys different principles than TNF-alpha-mediated apoptosis. Thus, in contrast to TNF-alpha-induced death, it is not accompanied by a decrease in the mitochondrial transmembrane potential and is not inhibited by preincubation with the antioxidant drug N-acetylcysteine. In synthesis, it appears that certain AIDS-associated mycoplasma species perturb the function and/or generation of cells from the myelomonocytic lineage via several distinct pathways.
Roussel Uclaf, Domaine Thérapeutique Immunologie, Romainville, France.
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G
Rawadi
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S
Roman-Roman
M
M
Castedo
V
V
Dutilleul
S
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Susin
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P
Marchetti
M
M
Geuskens
G
G
Kroemer
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001685:Biological Factors / Q000302:isolation & purification / Q000494:pharmacology; D002454:Cell Differentiation; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D018922:HL-60 Cells / Q000187:drug effects / Q000382:microbiology; D006358:Hot Temperature; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology* / Q000502:physiology; D008970:Molecular Weight; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology* / Q000502:physiology; D009175:Mycoplasma Infections / Q000150:complications / Q000276:immunology; D016858:Mycoplasma fermentans / Q000472:pathogenicity / Q000502:physiology*; D010587:Phagocytosis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D007213:Indomethacin