Induction of a Proinflammatory Cytokine Network byMycoplasma arthritidis-Derived Superantigen (MAS)

Abstract

Mycoplasma arthritidis is an arthritogenic organism for rodents, producing a superantigen (MAS). It has been postulated that mycoplasmas or superantigens thereof might play a role in human rheumatoid arthritis. Since M. arthritidis fulfills both, the present study was performed to investigate MAS-specific cytokine induction. Human or murine leukocytes were stimulated with MAS, staphylococcal enterotoxin E (SEE), or lipopolysaccharide (LPS). Cytokines were measured by ELISA, Bioassay, and RT-PCR. The response to MAS in humans was individually restricted, in contrast to the response to SEE or LPS. Furthermore, MAS showed the same capacity for inducing proinflammatory cytokines as interleukin (IL)-1 IL-6, and IL-8 as SEE and LPS. However, MAS showed a significantly decreased capacity to induce the anti-inflammatory cytokine IL-10 and IL-1RA. In mice, the reactivity to MAS was strictly MHC-II restricted, in contrast to that of SEE or LPS. The individual response to MAS in humans might be explained by the difference of the HLA-DR haplotype because H-2-differing mouse strains showed the same discrepancies. MAS induced an overproduction of proinflammatory cytokines, when its ability to induce proinflammatory and anti-inflammatory cytokines was compared with those of SEE and LPS. The individual response may explain an MHC linkage, and the failure to induce anti-inflammatory cytokines may be the reason for a chronic disease in contrast to acute inflammation.

Isolation and Partial Purification of Macrophage- and Dendritic Cell-Activating Components fromMycoplasma arthritidis: Association with Organism Virulence and Involvement with Toll-Like Receptor 2

“…Mycoplasma arthritidis secretes a superantigen, MAM, which is an activator of T cells and macrophages (7,38). Although LPS is not produced by M. arthritidis (40), it often occurs as a contaminant in the laboratory.…”

Binding of Mycoplasma arthritidis-derived mitogen to human MHC class II molecules via its N terminus is modulated by invariant chain expression and its C terminus is required for T cell activation

“…Over the past few years, mounting data support the possible involvement of various SAg in initiating and/or propagating human autoimmune diseases such as allergic encephalomyelitis, multiple sclerosis, insulindependent diabetes and rheumatoid arthritis (RA) [35][36][37][38][39]. Evidences that support the involvement of SAg such as MAM in the development of RA are (1) the corre-lation between the amplified V g subfamilies of TCR in the synovial fluid of RA patients and those being stimulated with MAM [40][41][42]; (2) the role of MHC class II in the susceptibility and severity of RA [43]; (3) the proliferation of MHC class II-positive cells and the accumulation of their activation products in the synovial fluid of RA patients [44][45][46]; and finally (4) the ability of SAg tot initiate cognate T/B cells interactions leading to B cell proliferation and differentiation [27,47] and to trigger the production of rheumatoid factors [48]. Based on these observations, and the ability of MAM to cause a spontaneous arthritis in rodents that resembles human RA, one can speculate that MAM or a MAM-like protein could be implicated in the development or RA.…”

Superantigen Genes Are More Important than theemmType for the Invasiveness of Group AStreptococcusInfection

“….05 toxins cause comprehensive (antigen-independent) activation of T cells. This induces massive secretion of inflammatory cytokines such as interferon g, interleukin 1, and tumor necrosis factor a [19][20][21][22]. Overproduction of these cytokines can lead to tissue damage, organ failure, and shock.…”