Interactions between Mycoplasmas and the Immune System

Abstract

Mycoplasmas are a heterogenous group of prokaryotic organisms causing a wide variety of diseases, including autoimmune disorders. Thus, it is not surprising that various mycoplasmas strains, including Mycoplasma arginini, M. arthritidis, M. neurolyticum and M. pulmonis, are able to regulate the immune response. Though some of the studies of the immunomodulatory action of mycoplasmas have been done in vivo, the majority of the investigations have been conducted in vitro. This has led to the recognition that mycoplasmas are polyclonal activators of both B and T cells from several species, acting through MHC-restricted or -unrestricted pathways. Mycoplasma activation not only induces T-cell proliferation but also leads but to the formation of cytotoxic T cells. We, as well as others, have shown that mycoplasma-mediated B-cell activation induces proliferation as well as Ig secretion, and also that mycoplasma stimulation of lymphocytes may result in the production of cytokines. We communicate here our investigations into the effects of an M. arginini strain on the growth and maturation of preactivated B cells. After an initial biological characterization of the M. arginini effects in vitro, we established the protein nature of the growth-supporting activity and proceeded further on to isolate and identify the responsible proteins. The use of lipid- and lipoglycan-free extracts has allowed us to further extend our studies on the biological activities of the proteins from M. arginini and to compare these results with the effects obtained using live organisms. Furthermore, the study was extended to include a characterization of the in vivo-induced effects of live M. arginini. Altogether, the results from these experiments allow us to conclude that M. arginini is a T-cell independent polyclonal B-cell mitogen, mediated by five identified proteins, inducing growth and Ig secretion of both resting and preactivated B cells.

Mycoplasma arginini enhances cytotoxicity of thioglycollate-elicited murine macrophages toward YAC-1 tumor cells through production of NO

“…37], and (3) the suppressive effect of activated macrophages on the proliferative responses of lymphocytes to mitogens or antigens is partially attributed to NO [38], it is possible that some of the features presented by immunodeficient patients may be ascribed to NO production induced by mycoplasma infections. Another aspect that deserves attention is the fact that misleading conclusions can be taken from in vitro experiments due to frequent and unnoticed contamination of cell cultures with mycoplasmas.…”

Time Course of Endothelial Cell Proliferation and Microvascular Remodeling in Chronic Inflammation

“…Mitogens from M. pulmonis organisms may directly affect endothelial cells as they do lymphocytes. [31][32][33] Endothelial cell mitogens may also come from activated epithelial cells. M. pulmonis organisms adhere to the luminal surface of the airway epithelium, creating a polarized stimulus that produces phenotypic and functional changes in endothelial cells on the surface of blood vessels facing the epithelium.…”

Molecular Biology and Pathogenicity of Mycoplasmas

“…On the other hand the ability of this Mycoplasma species to augment the activity of NK cells, known producers of IFN-␥ (243), may explain the observed in vivo production of IFN-␥ mRNA (122,318) in cells obtained from lung tissues. As mentioned above, it is doubtful whether T lymphocytes are mitogenically stimulated by M. pneumoniae, and it is still not clear whether M. arginini (397) stimulates T cells. Therefore, the observed capacity of these mycoplasmas to trigger IFN-␥ points to the possibility that mycoplasma-stimulated NK cells are responsible for IFN-␥ production.…”

“…Indeed, secretion of antibodies of different specificities, not related to mycoplasmal antigens, has been found in cultures of spleen cells exposed to various mycoplasmas possessing B-cell mitogens (91,397), including M. fermentans incognitus and M. penetrans (124). Polyclonal antibody production induced by mycoplasmas has been observed not only in vitro but also in vivo (91,309,397,420). It is worth noting that there is a clear segregation between mycoplasmainduced DNA synthesis and further differentiation of activated B cells into antibody-producing cells.…”