Excess production of interleukin-12 subunit p40 stimulated by the virulence plasmid of Salmonella enterica serovar Typhimurium in the early phase of infection in the mouse

The production of interleukin-12 (IL-12) and its subunits in response to Salmonella enterica serovar Typhimurium infection in the BALB/c mouse was examined. Unlike wild-type Typhimurium, a plasmidless strain, isolated by curing of the virulence plasmid (pSTV), did not stimulate excess IL-12p40 production. When a Tn5 tagged pSTV was transferred back to the plasmidless strain, the ability to stimulate IL-12p40 production was restored. However, a strain harbouring another Tn50pSTV failed to stimulate excess IL-12p40 production. This Tn5 insertion area, located on fragment H3 of pSTV, was designated spf (stimulation of protein forty). The ability to stimulate IL-12p40 production was restored in a partial diploid that carried a wild-type fragment covering the spf site. There is one known gene, repA, a locus, rsk, and two putative ORFs, in the vicinity of the Tn5 insertion site; however, these are not spf. The precise location of the spf locus is still unknown. (C) 2002 Academic Press.