IL-12 is dispensable for innate and adaptive immunity against low doses ofListeria monocytogenes

We have studied IL-12p35-deficient (IL-12p35(-/-)) mice to evaluate the rol e of IL-12 in resistance against Listeria monocytogenes, In the absence of bioactive IL-12p75, mutant mice acquired higher bacterial organ burden than wild-type mice and died during the first week following infection with nor mally sublethal doses of Listeria, Moreover, blood IFN-gamma levels were st rikingly reduced in mutant mice at day 2 post-infection. These results sugg est that in IL-12p35-deficient mice impaired production of IFN-gamma which is crucial for activation of listericidal effector functions of macrophages leads to defective innate immunity against Listeria, In contrast to mice d eficient for IFN-gamma or IFN-gamma receptor which are unable to resist ver y low infection doses of Listeria, IL-12p35-/- mice resisted up to 1000 c.f .u. and were able to eliminate Listeria, Spleen cells from mutant mice re-s timulated with heat-killed Listeria produced considerable amounts of IFN-ga mma, suggesting that at low dose infection sufficient IFN-gamma is produced independently of IL-12. Subsequent challenge of these immunized mice with high doses of L. monocytogenes resulted in sterile elimination demonstratin g efficient memory responses. These results demonstrate for the first time that at low doses of Listeria IL-12 is neither critical for innate immunity nor for the development of protective T cell-dependent acquired immunity.