Semi‐Purification of an Immunosuppressor Substance Secreted by Streptococcus mutans that Plays a Role in the Protection of the Bacteria in the Host

Abstract

Crude extracellular products of Streptococcus mutans (CEP-Sm) suppress the proliferative response to phytohaemagglutinin of human peripheral blood mononuclear cells and the primary immune response of C57BL/6 mice to sheep erythrocytes. This immunosuppressive effect favours the survival of the microorganism, and the bacteria lose the ability to secrete immunosuppressor substance if previously subcultured several times. Cells incubated with CEP-Sm and subsequently washed recover the ability to proliferate. Traces of CEP-Sm or to short a time of contact between CEP-Sm and the target immune system induced higher proliferative ratios or higher in vivo immune responses than controls, respectively. The proliferative values of cultures supplemented with CEP-Sm were parallel to the control values up to a certain time, after which they dropped abruptly. This drop is followed by a proliferation, and the higher the amount of CEP-Sm added to the cultures, the shorter the time until the proliferation. CEP-Sm was fractionated by means of ion exchange chromatography followed by double preparative isoelectrofocusing, ending in a subfraction of isoelectric point between 3.9 and 4.2, containing a heat-unstable material stainable by Coomassie blue but unstainable by periodic acid Schiff or methylene blue, and having a maximum optical density of 280 nm.

Increased resistance in BALB/c mice to reinfection with Candida albicans is due to immunoneutralization of a virulence-associated immunomodulatory protein

“…They are immunomodulatory because they are simultaneously mitogens for T-and B-lymphocytes and immunosuppressive for foreign antigens (Arala-Chaves et Ferreira et al, 1988;Lima et al, 1992;Pal & Horwitz, 1992;Ribeiro et al, 1991;Soares et al, 1990;Tavares et al, 1993). We have shown the importance of VIPs for the survival of pathogenic micro-organisms to be due to the fact that they potentiate microbial growth (Lima et al, 1992;Santarem et al, 1987;Tavares et al, 1993) and because mice immunized with VIPs become resistant to infection (Soares et al, 1990;Tavares et al, 1995).…”

“…We have previously observed that bacteria (Ferreira et al, 1997;Lima et al, 1992;Santarem et al, 1987), viruses and fungi (Tavares et al, 1993) secrete virulence-associated immunomodulatory proteins (VIPs). These VIPs are only produced by micro-organisms in their pathogenic form.…”

Identification of NAD+Synthetase fromStreptococcus sobrinusas a B-Cell-Stimulatory Protein

“…They induce polyclonal activation of lymphocytes, as well as the suppression of the host immune response to microbial specific antigens (8,19,39). It was also found that specific immunization against virulenceassociated immunomodulatory proteins (but not against other antigenic components of the microbe) induces immunoprotection (39,47). In a mouse model of Trypanosoma cruzi infection, a B-cell-mitogenic protein was isolated from the culture supernatants of the parasite infective forms.…”

“…It has been shown that different pathogenic microorganisms produce mitogenic and immunosuppressive proteins which also constitute important virulence factors (7,8,18,19,39). Such proteins have been generally designated virulence-associated immunomodulatory proteins.…”

“…The polyclonallymphocyte activation of the host, observed in several microbial infections, has been described as a general survival strategy of the infecting microorganism (9,21,30,48). Several microbial molecules have been described as B-and T-cell mitogens (8,16,19,25,27,31,35,39,40,49,50). It has been reported that S. sobrinus produces a protein that activates murine lymphocytes polyclonally, suppresses specific antibody response to S. sobrinus antigens, and potentiates the growth of the microorganism in the host (18).…”