Lipoxin-mediated inhibition of IL-12 production by DCs: a mechanism for regulation of microbial immunity.
Lipoxins are eicosanoid mediators that show potent inhibitory effects on the acute inflammatory process. We show here that the induction of lipoxin A(4) (LXA(4)) accompanied the in vivo suppression of interleukin 12 (IL-12) responsiveness of murine splenic dendritic cells (DCs) after microbial stimulation with an extract of Toxoplasma gondii. This paralysis of DC function could not be triggered in mice that were deficient in a key lipoxygenase involved in LXA(4) biosynthesis. In addition, DCs pre-treated with LXA(4) became refractory to microbial stimulation for IL-12 production in vitro and mice injected with a stable LXA(4) analog showed reduced splenic DC mobilization and IL-12 responses in vivo. Together, these findings indicate that the induction of lipoxins in response to microbial stimulation can provide a potent mechanism for regulating DC function during the innate response to pathogens.
Aliberti
J
J
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. jaliberti@niaid.nih.gov
Hieny
S
S
Reis e Sousa
C
C
Serhan
C N
CN
Sher
A
A
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000378:metabolism*; D003864:Depression, Chemical; D015536:Down-Regulation; D015777:Eicosanoids / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000502:physiology*; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D044045:Lipoxins; D051379:Mice; D008810:Mice, Inbred C57BL; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000235:genetics; D013154:Spleen / Q000166:cytology; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology*
D015777:Eicosanoids; D006893:Hydroxyeicosatetraenoic Acids; D008070:Lipopolysaccharides; D044045:Lipoxins; D019713:Receptors, CCR5; C040527:lipoxin A4; D018664:Interleukin-12; D001094:Arachidonate 5-Lipoxygenase