Interleukin-13-Mediated Paneth Cell Degranulation and Antimicrobial Peptide Release

Interleukin-13-Mediated Paneth Cell Degranulation and Antimicrobial Peptide Release
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Interleukin-13 介导的潘氏细胞脱颗粒和抗菌肽释放

DOI:
10.1159/000357644
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发表时间:
2014
影响因子:
5.3
通讯作者:
Hornef
Hornef
中科院分区:
医学2区
文献类型:
--
作者:
Stockinger;Albers;Ménard;Pütsep;Andersson;Dupont;Hornef

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潘氏细胞来源的肠源性抗菌肽显著有助于抗菌宿主防御和宿主-微生物稳态。通过酶促加工和释放到小肠腔中进行调节,但所涉及的刺激尚不完全清楚。在这里,各种微生物和免疫刺激诱导抗菌肽从小肠组织释放的能力进行了系统的评价,使用抗菌活性测试,免疫染色潘氏细胞颗粒和质谱。我们证实了毒蕈碱受体激动剂卡巴胆碱和核苷酸结合寡聚化结构域配体胞壁酰二肽的刺激活性。相反,在用Toll样受体配体poly(I:C)、脂多糖或CpG以及细胞因子白细胞介素(IL)-15、IL-22、IL-28和干扰素-γ处理后,没有观察到抗菌活性的释放。然而,在用内源性介质IL-4和IL-13刺激后观察到快速潘氏细胞脱粒和抗菌活性释放。这一过程需要磷脂酰肌醇3-激酶,并与帕内特细胞中的蛋白激酶B磷酸化有关。流式细胞术分析证实分离的Paneth细胞上表达IL-13受体α1。我们的研究结果确定了IL-13作为潘氏细胞脱粒和肠道抗菌肽释放的诱导剂的新作用。因此,IL-13可能有助于粘膜抗微生物宿主防御和宿主微生物体内平衡。
Paneth cell-derived enteric antimicrobial peptides significantly contribute to antibacterial host defense and host-microbial homeostasis. Regulation occurs by enzymatic processing and release into the small intestinal lumen, but the stimuli involved are incompletely understood. Here, the capacity of various microbial and immune stimuli to induce antimicrobial peptide release from small intestinal tissue was systematically evaluated using antibacterial activity testing, immunostaining for Paneth cell granules and mass spectrometry. We confirmed the stimulatory activity of the muscarinic receptor agonist carbachol and the nucleotide-binding oligomerization domain ligand muramyl dipeptide. In contrast, no release of antibacterial activity was noted after treatment with the Toll-like receptor ligands poly (I: C), lipopolysaccharide or CpG, and the cytokines interleukin (IL)-15, IL-22, IL-28 and interferon-γ. Rapid Paneth cell degranulation and antimicrobial activity release, however, was observed after stimulation with the endogenous mediators IL-4 and IL-13. This process required phosphatidylinositol 3-kinase and was associated with protein kinase B phosphorylation in Paneth cells. Flow cytometric analysis confirmed expression of the IL-13 receptor α1 on isolated Paneth cells. Our findings identify a novel role of IL-13 as inducer of Paneth cell degranulation and enteric antimicrobial peptide release. IL-13 may thus contribute to mucosal antimicrobial host defense and host microbial homeostasis.
DOI: 10.1016/s1074-7613(00)80477-x
发表时间: 1998-02-01
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Ayabe T 等人:“肠道潘氏细胞响应细菌分泌杀微生物的 α-防御素。”《自然免疫》。
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