IL-12 is dispensable for innate and adaptive immunity against low doses of Listeria monocytogenes.
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-gamma 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-gamma 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-gamma or IFN-gamma 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-gamma, 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 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.
Brombacher
F
F
Max-Planck-Institute for Immunobiology, Freiburg, Germany.
Dorfmüller
A
A
Magram
J
J
Dai
W J
WJ
Köhler
G
G
Wunderlin
A
A
Palmer-Lehmann
K
K
Gately
M K
MK
Alber
G
G
D000818:Animals; D003433:Crosses, Genetic; D006099:Granuloma; D007109:Immunity; D007113:Immunity, Innate; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology* / Q000401:mortality; D008099:Liver / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination
D018664:Interleukin-12; D007371:Interferon-gamma