International Immunology, Vol. 11, No. 3, 325-332,
March 1999
© 1999 Japanese Society for Immunology
IL-12 is dispensable for innate and adaptive immunity against low doses of Listeria monocytogenes
Max-Planck-Institute for Immunobiology, Stübeweg 51, 79108 Freiburg, Germany
1 Department of Inflammation/Autoimmune Diseases, Hoffmann-La Roche Inc., Nutley, NJ 07110-1199, USA
2 Department of Pathology, Albert-Ludwig-University of Freiburg, 79104 Freiburg, Germany
3 Department of Infectious Diseases, F. Hoffmann-La Roche AG, 4070 Basel, Switzerland
Correspondence to: G. Alber, University of Leipzig, Zwickauer Strasse 53, 04103 Leipzig, Germany
We have studied IL-12p35-deficient (IL-12p35–/–) mice to evaluate the role 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 normally sublethal doses of Listeria. Moreover, blood IFN-
levels were strikingly reduced in mutant mice at day 2 post-infection. These results suggest that in IL-12p35-deficient mice impaired production of IFN- which is crucial for activation of listericidal effector functions of macrophages leads to defective innate immunity against Listeria. In contrast to mice deficient for IFN- or IFN- receptor which are unable to resist very 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-stimulated with heat-killed Listeria produced considerable amounts of IFN-, suggesting that at low dose infection sufficient IFN- is produced independently of IL-12. Subsequent challenge of these immunized mice with high doses of L. monocytogenes resulted in sterile elimination demonstrating 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.
Keywords: cytokines, infection, T lymphocytes, Th1, Th2
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