INTRACELLULAR SALMONELLA-DUBLIN INDUCES SUBSTANTIAL SECRETION OF THE 40-KILODALTON SUBUNIT OF INTERLEUKIN-12 (IL-12) BUT MINIMAL SECRETION OF IL-12 AS A 70-KILODALTON PROTEIN IN MURINE MACROPHAGES

The induction by intracellular pathogens of interleukin-12 (IL-12) sec retion is of particular importance since this cytokine has been shown to be necessary for optimal cell-mediated immune responses, Several re cent investigations have suggested that cultured macrophages are a sig nificant source of IL-12 following intracellular infection with pathog ens such as Salmonella spp, In an effort to critically evaluate the ma gnitude of the IL-12 response in cultured macrophages following intera ction with Salmonella dublin, enzyme-linked immunosorbent assays speci fic for the 40- and 70-kDa subunits of IL-12 (IL-12p40 and IL-12p70) a nd a sensitive bioassay for IL-12p40 were used, Using BALB/c macrophag es, S. dublin at various challenge doses was a potent inducer of IL-12 p40 secretion (>6,000 pg/10(7) macrophages). However when secretion of IL-12p70 was evaluated, S. dublin did not induce comparable IL-12p70 production (<80 pg/10(7) macrophages) at any time, despite varying the challenge dose of Salmonella. The limited ability of BALB/c (Ity(s)) macrophages to secrete IL-12p70 in response to Salmonella was not a st rain-specific phenomenon since similar results were demonstrated for m acrophages isolated from CBA/J (Ity(r)) and C3H/HeJ (lipopolysaccharid e [LPS]-hyporesponsive) mice. While intracellular infection with Salmo nella was not a potent stimulus for IL-12p70 secretion in these mouse strains, macrophages from these mice responded significantly to a stim ulus of gamma interferon plus LPS, Taken together these results demons trate a limited capacity for intracellular Salmonella to stimulate mur ine macrophage secretion of IL-12p70, despite being a significant stim ulus for IL-12p40 secretion, Furthermore, our results suggest that Sal monella-induced IL-12p10 secretion by macrophages is not solely an LPS -mediated event.