Leukotrienes Are Potent Adjuvant during Fungal Infection: Effects on Memory T Cells
Leukotrienes Are Potent Adjuvant during Fungal Infection: Effects on Memory T Cells
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DOI：
10.4049/jimmunol.181.12.8544
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发表时间：
2008-12-15
影响因子：
4.4
通讯作者：
Faccioli, Lucia H.
中科院分区：
文献类型：
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作者：
Medeiros, Alexandra I.;Sa-Nunes, Anderson;Faccioli, Lucia H.
白三烯（LT）是参与控制宿主防御的有效脂质介质。LTB 4诱导白细胞积聚，增强吞噬作用和细菌清除，并增加NO合成。LTB 4在由LTB 4受体1（LTB 4的高亲和力受体）介导的早期效应T细胞募集中也很重要。本研究的目的是评价LT是否参与了荚膜组织胞浆菌感染小鼠模型中对疫苗接种的二次免疫应答。我们的结果表明，保护野生型小鼠免疫与无细胞抗原从H。荚膜梭菌对组织胞浆菌病的抑制作用与LTB 4和IFN-γ产生的增加以及记忆T细胞向肺中的募集有关。相比之下，无细胞Ag免疫小鼠缺乏5-脂氧合酶（-/-），一种参与LT合成的关键酶，显示记忆T细胞向肺的募集显著减少，与TGF-β和IL-10的合成增加相关。引人注目的是，这些作用与5-脂氧合酶（-/-）感染小鼠的死亡率增加有关。这些数据确立了LT在组织胞浆菌病的原发性和继发性免疫应答中的重要免疫调节作用。免疫学杂志，2008，181：8544-8551.
Leukotrienes (LTs) are potent lipid mediators involved in the control of host defense. LTB4 induces leukocyte accumulation, enhances phagocytosis and bacterial clearance, and increases NO synthesis. LTB4 is also important in early effector T cell recruitment that is mediated by LTB4 receptor 1, the high-affinity receptor for LTB4. The aims of this study were to evaluate whether LTs are involved in the secondary immune response to vaccination in a murine model of Histoplasma capsulatum infection. Our results demonstrate that protection of wild-type mice immunized with cell-free Ags from H. capsulatum against histoplasmosis was associated with increased LTB4 and IFN-gamma production as well as recruitment of memory T cells into the lungs. In contrast, cell-free Ag-immunized mice lacking 5-lipoxygenase(-/-), a critical enzyme involved in LT synthesis, displayed a marked decrease on recruitment of memory T cells to the lungs associated with increased synthesis of TGF-beta as well as IL-10. Strikingly, these effects were associated with increased mortality to 5-lipoxygenase(-/-)-infected mice. These data establish an important immunomodulatory role of LTs, in both the primary and secondary immune responses to histoplasmosis. The Journal of Immunology, 2008,181: 8544-8551.