Parasite Clearance in Leishmaniasis in Resistant Animals Is Independent of the IL-23/IL-17A Axis.
Parasite Clearance in Leishmaniasis in Resistant Animals Is Independent of the IL-23/IL-17A Axis.
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抗性动物利什曼病的寄生虫清除与 IL-23/IL-17A 轴无关
DOI：
10.1016/j.jid.2016.05.111
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发表时间：
1908
期刊：
影响因子：
--
通讯作者：
von Stebut E
中科院分区：
文献类型：
--
作者：
Dietze-Schwonberg K;Lorenz B;Lopez Kostka S;Waisman A;von Stebut E
利什曼病是一种由沙蝇叮咬引起的寄生虫病。根据世界卫生组织(世卫组织)的数据，90多个国家有1200万人感染，每年报告130万新病例，每年约有3万人死亡(世卫组织，2015年)。在它们的血餐期间，雌性沙蝇将感染阶段的前鞭毛体传播到宿主(例如，啮齿动物或人)的皮肤中(Sack和Noben-Trauth，2002)。在这里，前鞭毛体主要由巨噬细胞和中性粒细胞摄取(Woelping等人，2006年)。在巨噬细胞内部，前鞭毛体转变为细胞内的无鞭毛体，并进行复制。释放的无鞭毛体随后被树突状细胞等其他抗原提呈细胞吸收。感染的树突状细胞迁移到引流淋巴结，在C57BL/6小鼠和人类等免疫活性宿主中，它们激活CD4+T辅助1型(Th1)和CD8+细胞毒性T细胞分泌干扰素-γ，进而导致感染的巨噬细胞一氧化氮上调，最终杀死细胞内寄生虫。另一方面，在免疫抑制的宿主和BALB/c小鼠中，无鞭毛体激活的树突状细胞诱导主要的Th2/调节性T细胞/Th17免疫反应(Biedermann等人，2001，Lopez Kostka等人，2009，Sack和Noben-Trauth，2002，Suffia等人，2005)，最终导致疾病进展。IL-17A的主要来源是CD4+T细胞(在两个菌株中)，但在BALB/c小鼠中，病变浸润性中性粒细胞也产生相当数量的IL-17A，有助于CCL3介导的持续性中性粒细胞渗透(Lopez Kostka等人，2009年)。同样，BALB/c IL-17A−/−小鼠与中性粒细胞耗尽的BALB/c小鼠一样，受到保护，免受进行性疾病的侵袭(Tacchini-Cottier等人，2000年)。我们发现从感染的BALB/c小鼠分离的淋巴结细胞中Th17诱导的IL-23p19水平高于从C57BL/6分离的细胞，但IL-12p40、IL-6和转化生长因子-β的水平相同，提示树突状细胞来源的IL-23p19诱导BALB/c小鼠Th17的诱导。
Leishmaniasis is a parasitic disease caused by the bite of a sand fly. According to the World Health Organization (WHO), 12 million people in more than 90 countries are infected, 1.3 million new cases are reported per year, and approximately 30,000 die annually (WHO, 2015). During their blood meal, female sand flies transmit infectious-stage promastigotes into the skin of the host (eg, rodents or humans)(Sacks and Noben-Trauth, 2002). Here, promastigotes are mainly ingested by macrophages and neutrophils (Woelbing et al., 2006). Inside the macrophages, promastigotes transform into the intracellular amastigote life form and replicate. Released amastigotes are then taken up by other antigen-presenting cells such as dendritic cells. The infected dendritic cells migrate to draining lymph nodes, where in immunocompetent hosts such as C57BL/6 mice and humans, they activate CD4+ T helper type 1 (Th1) and CD8+ cytotoxic T cells to secrete IFN-γ, which in turn leads to upregulation of nitric oxide in infected macrophages that finally kill the intracellular parasite. On the other hand, in immunosuppressed hosts and in BALB/c mice, dendritic cell activation by amastigotes induces a predominant Th2/regulatory T cell/Th17 immune response (Biedermann et al., 2001, Lopez Kostka et al., 2009, Sacks and Noben-Trauth, 2002, Suffia et al., 2005), which eventually leads to disease progression.Previously, we observed that IL-17A levels are increased in infected BALB/c mice as compared to infected C57BL/6 mice. The main sources of IL-17A were CD4+ T cells (in both strains), but in BALB/c mice, lesion infiltrating neutrophils also produced considerable amounts of IL-17A contributing to CCL3-mediated persisting neutrophil infiltrates (Lopez Kostka et al., 2009). In line, BALB/c IL-17A−/− mice were protected from progressive disease similar to neutrophil-depleted BALB/c mice (Tacchini-Cottier et al., 2000). We found elevated levels of Th17-inducing IL-23p19 in lymph node cells isolated from infected BALB/c mice as compared to cells isolated from C57BL/6, but equal amounts of IL-12p40, IL-6, and transforming growth factor-β, suggesting that dendritic cell-derived IL-23p19 induces Th17 induction in BALB/c mice.
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影响因子：
15.9
作者：
Haak, Stefan;Croxford, Andrew L.;Waisman, Ari
通讯作者：
Waisman, Ari
影响因子：
30.5
作者：
Biedermann, T;Zimmermann, S;Röcken, M
通讯作者：
Röcken, M
影响因子：
4.4
作者：
Tacchini-Cottier, F;Zweifel, C;Louis, JA
通讯作者：
Louis, JA
胃分泌随着年龄的增长而减少：进一步观察。
影响因子：
15.9
作者：
Arthur L. Bloomfield
通讯作者：
Arthur L. Bloomfield