Heat-killed Streptococcus suis capsular type 2 strains stimulate tumor necrosis factor alpha and interleukin-6 production by murine macrophages

Streptococcus suis capsular type 2 is an important etiological agent of swi ne meningitis, and it is also a zoonotic agent. Since mononuclear phagocyte s have been suggested to play a central role in the pathogenesis of meningi tis, the objective of the present study was to evaluate the capacity of who le killed S, suis type 2 organisms to induce the release of the proinflamma tory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (I L-6) by murine macrophages, Induction of cytokines was evaluated in the pre sence or absence of phorbol ester (phorbol 12-myristate 13-acetate [PMA]) c ostimulation. Results show ed that S. suis type 2 stimulated the production of both cytokines in a concentration- and time-dependent fashion. Although large doses of bacteria were required for maximal cytokine release, titers were similar to those obtained with the lipopolysaccharide (LPS) positive control, An increase in cytokine release was observed with both S. suis and LPS with PMA costimulation, Experiments with cytochalasin-treated macropha ges showed that the stimulation of cytokine production was phagocytosis ind ependent. When macrophages were stimulated with an unencapsulated mutant, a n increase in TNF production was observed, but the absence of the capsule h ad no effect on IL-6 production. In fact, whereas purified capsular polysac charide of S. suis failed to induce cytokine release, purified S. suis cell wall induced both TNF and, to a lesser extent, IL-6, IL-6 secretion probab ly requires some distinct stimuli which differ from those of TNF, Finally, the S, suis putative virulence factors suilysin and extracellular protein E F showed no cytokine-stimulating activity, The ability of S. suis to trigge r macrophages to produce proinflammatory cytokines may have an important ro le in the initiation and development of meningitis caused by this microorga nism.