Immune suppression induced by Actinobacillus actinomycetemcomitans: effects on immunoglobulin production by human B cells

Abstract

Actinobacillus actinomycetemcomitans produces an immunosuppressive factor (ISF) which has been shown to suppress mitogen- and antigen-induced DNA, RNA, and protein synthesis in human T lymphocytes. In this study, we examined purified A. actinomycetemcomitans ISF for its ability to alter immunoglobulin production by human B cells. The ISF caused a dose-dependent inhibition of pokeweed mitogen (PWM)-induced immunoglobulin G (IgG) and IgM production. Preexposure to ISF was not required to achieve maximal inhibition of immunoglobulin synthesis, as previously observed for its effect on T-cell activation. Nevertheless, the ISF appeared to act by irreversibly affecting the early stages of cell activation. While PWM-induced immunoglobulin production is under the influence of T-regulatory circuits, it appears that the ISF interacts directly with B cells. First, ISF failed to alter either the synthesis of interleukin-2 (IL-2) or the expression of IL-2 receptors on T cells. Second, experiments in which individual purified populations of cells were exposed to ISF, washed, and placed back into tissue culture indicated that when all cells (i.e., T cells, B cells, and monocytes) were exposed to ISF, significant suppression was observed. However, when only one cell population was treated with ISF, suppression of both IgG and IgM synthesis was observed only when the B-cell-enriched population was exposed to ISF. These results in conjunction with our earlier findings suggest that the ISF functions via the activation of a regulatory subpopulation of B lymphocytes, which in turn either directly or indirectly (via suppressor T cells) downregulate both B- and T-cell responsiveness. Furthermore, it is hypothesized that patients who harbor A. actinomycetemcomitans could suffer from local or systemic immune suppression. This suppression may enhance the pathogenicity of A. actinomycetemcomitans itself or that of some other opportunistic organism.

Host responses induced by co‐infection with Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans in a murine model

“…This suggests that the observed augmented response to P. gingivalis resulted from co-infection with A. actinomycetemcomitans. Failure to detect antibody to A. actinomycetemcomitans may be due to an inhibitory effect of this organism on immunoglobulin production, as reported by Shenker et al (33). However, by day 20 after infection, mice produced antibodies to A. actinomycetemcomitans, and no difference was seen i*" the levels of anti-A.…”

“…The suppressing mechanism appeared to be due to blocking of the normal cell cycle before Gl. Finally, the decrease in responses may be due to a heat-labile immunosuppressive factor produced by A. actinomycetemcomitans (31,33) and possibly P. gingivalis. Additional studies are needed to determine whether one of these mechanisms or another are responsible for the decreased mitogenic responses observed in spleen cell cultures from mice injected with P. gingivalis and/or A. actinomycetemcomitans.…”

“…The lipopolysaccharide from this bacterium has the potential to resorb bone (20) and to act as a Bcell mitogen (15,43). Furthermore, a heat-labile immunosuppressive factor also produced by A. actinomycetemcomitans has been shown to inhibit DNA, RNA and protein synthesis in lymphocytes (31) and immunoglobulin synthesis by B cells (33). In a co-inoculation study, it was shown that injection of mice with Campylobacter rectus and A. actinomycetemcomitans resulted in a more severe infection than seen in monoinfected mice (9).…”

Virulence factors of Actinobacillus actinomycetemcomitans relevant to the pathogenesis of inflammatory periodontal diseases

“…Shenker et al [62] have isolated a 60-kDa protein from the organism that inhibits (IDs0 = 50 ng/ml) IgG and IgM synthesis by human peripheral blood lymphocytes (HPBL) in response to mitogens. The protein is claimed to exert its effect by activating a regulatory subpopulation of B cells which downregulates B and T cell responsiveness via 'suppressor' T cells.…”

Immunosuppressive effect induced by Actinobacillus actinomycetemcomitans: effect on immunoglobulin production and lymphokine synthesis

“…Studies are accumulating that suggest that a cotnponent of A. actinotnvcetetticomitatis is capable of inducing significant immunosuppression. A. actinomycetemcomitans produce ISF capable of depressing human peripheral blood lymphocyte proliferative responses to both tnitogens and antigens (25,26). Leukotoxin from A. actinotnycetemcomitans also induces immunosuppression by subverting monocytes (20).…”