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) secretion is of particular importance since this cytokine has been shown to be necessary for optimal cell-mediated immune responses. Several recent investigations have suggested that cultured macrophages are a significant source of IL-12 following intracellular infection with pathogens such as Salmonella spp. In an effort to critically evaluate the magnitude of the IL-12 response in cultured macrophages following interaction with Salmonella dublin, enzyme-linked immunosorbent assays specific for the 40- and 70-kDa subunits of IL-12 (IL-12p40 and IL-12p70) and a sensitive bioassay for IL-12p70 were used. Using BALB/c macrophages, S. dublin at various challenge doses was a potent inducer of IL-12p40 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 strain-specific phenomenon since similar results were demonstrated for macrophages isolated from CBA/J (Ity(r)) and C3H/HeJ (lipopolysaccharide [LPS]-hyporesponsive) mice. While intracellular infection with Salmonella was not a potent stimulus for IL-12p70 secretion in these mouse strains, macrophages from these mice responded significantly to a stimulus of gamma interferon plus LPS. Taken together these results demonstrate a limited capacity for intracellular Salmonella to stimulate murine macrophage secretion of IL-12p70, despite being a significant stimulus for IL-12p40 secretion. Furthermore, our results suggest that Salmonella-induced IL-12p40 secretion by macrophages is not solely an LPS-mediated event.
Bost
K L
KL
Department of Microbiology and Immunology, Tulane University Medical Center, New Orleans, Louisiana 70112, USA. kbost@tmcpop.tmc.tulane.edu
Clements
J D
JD
D000818:Animals; D002478:Cells, Cultured; D018664:Interleukin-12 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D008970:Molecular Weight; D012475:Salmonella / Q000502:physiology*
D008070:Lipopolysaccharides; D018664:Interleukin-12