Helicobacter pylori Stimulates Dendritic Cells To Induce Interleukin-17 Expression from CD4+ T Lymphocytes
Helicobacter pylori Stimulates Dendritic Cells To Induce Interleukin-17 Expression from CD4+ T Lymphocytes
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DOI：
10.1128/iai.00524-09
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发表时间：
2010-02-01
影响因子：
3.1
通讯作者：
Lombardi, Giovanna
中科院分区：
文献类型：
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作者：
Khamri, Wafa;Walker, Marjorie M.;Lombardi, Giovanna
幽门螺杆菌是一种人类胃十二指肠病原体，可导致活动性慢性炎症，其特征是 T 细胞反应偏向 Th1 表型。人们普遍认为幽门螺杆菌感染会诱导 Th17 反应。在粘膜部位，树突状细胞 (DC) 具有诱导效应 T 细胞的能力。在这里，我们评估 DC 在幽门螺杆菌诱导的白细胞介素 17 (IL-17) 反应中的作用。对人胃粘膜活检样本进行免疫组织化学和免疫荧光检查，结果显示幽门螺杆菌感染患者中的髓样 DC 与 IL-23 共定位，并且幽门螺杆菌感染的胃窦活检样本中存在产生 IL-17 的淋巴细胞。与此同时，在体外用活幽门螺杆菌细胞刺激的人单核细胞衍生的 DC 在没有 IL-12 释放的情况下产生显着水平的 IL-23。随后将幽门螺杆菌感染的 DC 与自体 CD4(+) T 细胞一起孵育，导致γ干扰素 (IFN-γ) 和 IL-17 的表达。 IL-1 和 IL-23 的抑制在较小程度上抑制了 T 细胞产生 IL-17。最后，不表达主要毒力因子的等基因幽门螺杆菌突变株在诱导 DC 释放 IL-1 和 IL-23 以及 T 细胞释放 IL-17 方面的效果不如亲本菌株。总而言之，我们可以得出结论，DC 是幽门螺杆菌刺激后 IL-23/IL-17 表达的有效诱导剂。 IL-1/IL-23 以及幽门螺杆菌毒力因子似乎在介导这种反应中发挥着重要作用。
Helicobacter pylori is a human gastroduodenal pathogen that leads to active chronic inflammation characterized by T-cell responses biased toward a Th1 phenotype. It has been accepted that H. pylori infection induces a Th17 response. At mucosal sites, dendritic cells (DCs) have the capacity to induce effector T cells. Here, we evaluate the role of DCs in the H. pylori-induced interleukin-17 (IL-17) response. Immunohistochemistry and immunofluorescence were performed on human gastric mucosal biopsy samples and showed that myeloid DCs in H. pylori-infected patients colocalized with IL-23- and that IL-17-producing lymphocytes were present in H. pylori-infected antral biopsy samples. In parallel, human monocyte-derived DCs stimulated in vitro with live H. pylori cells produced significant levels of IL-23 in the absence of IL-12 release. The subsequent incubation of H. pylori-infected DCs with autologous CD4(+) T cells led to gamma interferon (IFN-gamma) and IL-17 expression. The inhibition of IL-1 and, to a lesser extent, IL-23 inhibited IL-17 production by T cells. Finally, isogenic H. pylori mutant strains not expressing major virulence factors were less effective in inducing IL-1 and IL-23 release by DCs and IL-17 release by T cells than parental strains. Altogether, we can conclude that DCs are potent inducers of IL-23/IL-17 expression following H. pylori stimulation. IL-1/IL-23 as well as H. pylori virulence factors seem to play an important role in mediating this response.