Modulation of the immune system by Neisseria meningitidis.

Abstract

The immunomodulatory potential of Neisseria meningitidis was investigated. Spleen cells from mice injected intraperitoneally with low to moderate doses of meningococci (10(4)-10(7)) were found to display enhanced responses to the mitogens lipopolysaccharide (LPS), phytohaemagglutinin (PHA), and concanavalin A (Con A). In contrast, high doses of meningococci (10(8)-10(9)) caused a marked decrease in mitogenic reactivity. Meningococci-injected mice also displayed a dose-dependent suppression of a primary anti-sheep red blood cell (SRBC) plaque-forming cell (PFC) response. The timing between the injection of SRBC and of meningococci appeared to play an important role in the induction of suppression by the organisms. Thus, decreased PFC responses were observed only when the bacteria were injected prior to the antigen. When meningococci were injected at the same time or after SRBC, normal or even increased PFC responses developed. Kinetic experiments showed that the onset of suppression of both mitogen and antibody responses by meningococci was very rapid, so that by 6-7 h after injection of the bacteria, mice showed markedly reduced mitogen responses and became essentially unable to mount an antibody response against SRBC. Suppression of mitogen responses was relatively transient, since reactivity returned to normal after 48 h. However, the ability of infected animals to mount a normal anti-SRBC response did not fully return until 12 days after the infection. Spleen cells from meningococci-infected mice also showed markedly depressed PFC responses when stimulated with SRBC in vitro but failed to suppress the response of normal spleen cells in mixed cultures. These observations indicate that putative suppressor cells, if they exist at all, are too insignificant in terms of numbers and/or efficiency to account for the observed immunosuppression. A more likely explanation for the inhibition, which is supported by our data, presented here and elsewhere, is that certain surface components of meningococci are capable of imparting immunosuppressive signals directly onto target lymphocytes.