L Leishmania major are intramacrophage parasite whose eradication requires the induction of T helper 1(Th1)effector cells.Interleukin 12(IL-12) mediates Th1 effector cells development and enhances interferon γproduct...L Leishmania major are intramacrophage parasite whose eradication requires the induction of T helper 1(Th1)effector cells.Interleukin 12(IL-12) mediates Th1 effector cells development and enhances interferon γproduction by T cells and natural killer cells.Infection of macrophages in vitro by promastigotes of L. major caused no IL-12 p40 transcripts. Using competitor construct to quantitate a number of transcripts, a kinetic analysis of cytokine induction during the first few days of infection by L. major was performed.In resistant mice,the transcripts for IL-2, IL-4 and IL-10 were subsequently downregulated, whereas in susceptible mice,these transcripts were only slightly decreased, and IL4 continued to be reexpressed at high levels. IL-12 transcripts were first detected in vivo by 7 d after infection.Challenge of macrophages in vitro confirmed that amastigotes induced IL-12 p40 mRNA.Reexamination of the cytokine rnRNA at 4d revealed expression of IL-13 in all strains analyzed,suggesting that IL-2 and IL-13 may mediate the IL-12independent production of IFN-γ during the first days after infection. Leishmania have evolved to avoid inducing IL-12 from host macrophages during transmission from the insect vector, and cause a striking induction of mRNAs for IL-2, IL-4, IL-10, and IL-13 in CD+4T cells. Each of these activities may favor survival of the organism.展开更多
文摘L Leishmania major are intramacrophage parasite whose eradication requires the induction of T helper 1(Th1)effector cells.Interleukin 12(IL-12) mediates Th1 effector cells development and enhances interferon γproduction by T cells and natural killer cells.Infection of macrophages in vitro by promastigotes of L. major caused no IL-12 p40 transcripts. Using competitor construct to quantitate a number of transcripts, a kinetic analysis of cytokine induction during the first few days of infection by L. major was performed.In resistant mice,the transcripts for IL-2, IL-4 and IL-10 were subsequently downregulated, whereas in susceptible mice,these transcripts were only slightly decreased, and IL4 continued to be reexpressed at high levels. IL-12 transcripts were first detected in vivo by 7 d after infection.Challenge of macrophages in vitro confirmed that amastigotes induced IL-12 p40 mRNA.Reexamination of the cytokine rnRNA at 4d revealed expression of IL-13 in all strains analyzed,suggesting that IL-2 and IL-13 may mediate the IL-12independent production of IFN-γ during the first days after infection. Leishmania have evolved to avoid inducing IL-12 from host macrophages during transmission from the insect vector, and cause a striking induction of mRNAs for IL-2, IL-4, IL-10, and IL-13 in CD+4T cells. Each of these activities may favor survival of the organism.
