Alterations of intralesional and lymph node gene expression and cellular composition induced by IL-12 administration during leishmaniasis.
Changes in gene expression and cellular distribution in the lymph node and at the site of infection, the footpad, during Leishmania major infection and/or IL-12 administration were evaluated. Otherwise susceptible BALB/c mice given IL-12 are able to resolve infection. Interestingly, iNOS was not induced in the lymph node by IL-12, yet, nitric oxide is critical in the control of leishmaniasis. However, we observed an increase in iNOS at the lesion site in response to IL-12. These results reflect the importance of examining the primary site of infection. We observed no changes in inflammation at the lesion site; however, IL-12 promoted an early inflammatory response in the lymph nodes. IL-12 administration differentially affected both the local and systemic immune response to invading leishmanial parasites. IL-12 induced iNOS at the lesion site and an early granulomatous inflammation in the lymph node; therefore, we hypothesize that these are key events responsible for the resolution of disease in BALB/c mice treated with IL-12.
Genetics Institute, Inc., Department of Preclinical Biology, Andover, MA, USA.
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Schopf
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Erickson
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Hayes
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Chung
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Lavigne
J
J
Sypek
D000818:Animals; D016207:Cytokines / Q000032:analysis / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005528:Foot; D006651:Histocytochemistry; D018664:Interleukin-12 / Q000008:administration & dosage*; D007378:Interleukins / Q000235:genetics / Q000302:isolation & purification; D018320:Leishmania major / Q000276:immunology / Q000302:isolation & purification; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000096:biosynthesis; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D013194:Staining and Labeling
D016207:Cytokines; D007378:Interleukins; D012333:RNA, Messenger; D018664:Interleukin-12; D012313:RNA; D019001:Nitric Oxide Synthase