Correction for Cobo et al., "Entamoeba histolytica Alters Ileal Paneth Cell Functions in Intact and Muc2 Mucin Deficiency".
Correction for Cobo et al., "Entamoeba histolytica Alters Ileal Paneth Cell Functions in Intact and Muc2 Mucin Deficiency".
复制标题
对 Cobo 等人的更正，“溶组织内阿米巴改变完整的回肠潘氏细胞功能和 Muc2 粘蛋白缺乏症”。
DOI：
10.1128/iai.00564-18
复制
发表时间：
2018
影响因子：
3.1
通讯作者：
Chadee,Kris
中科院分区：
文献类型：
--
作者：
Cobo,EduardoR;Holani,Ravi;Moreau,France;Nakamura,Kiminori;Ayabe,Tokiyoshi;Mastroianni,JenniferR;Eriguchi,Yoshihiro;Ouellette,Andre;Chadee,Kris
肠道α防御素，在小鼠中被称为隐蛋白(CRP)，以及潘氏细胞分泌的溶菌酶，有助于回肠固有的宿主防御。包括溶菌酶和β防御素在内的抗菌因子通常嵌入杯状细胞分泌的肠腔糖基化结肠粘蛋白2中，形成对肠道稳态和病原体入侵至关重要的保护性粘液层。在这项研究中，我们通过在Muc2+/+和Muc2−/−的封闭回肠循环中接种寄生虫，并定量测定潘氏细胞的定位(溶菌酶表达)和功能(C反应蛋白的分泌)，研究了回肠天然免疫对肠道阿米巴病的病原体内阿米巴的作用。相对于Muc2+/+分枝杆菌，Muc2−/−分枝杆菌表现出松散的潘氏细胞错位分布，在隐窝和绒毛中溶菌酶分泌增加，以响应溶组性肠杆菌。抑制半乳糖和EhCP5阴性的内阿米巴溶组织半胱氨酸蛋白酶5(EhCP5)结合的半乳糖/半乳糖凝集素对寄生虫诱导的潘氏细胞溶菌酶的合成没有影响。尽管Muc2−/−小鼠对溶组织埃希氏菌的反应中，Crp基因的基础回肠表达没有受到影响，但肠腔渗出物中也存在促炎症细胞因子和C反应蛋白多肽分泌。有趣的是，溶组埃希氏菌分泌的半胱氨酸蛋白酶能切割Crp4的前区，但不能切割活性形式。这些发现将Muc2粘蛋白定义为回肠屏障功能的重要组成部分，该功能调节Paneth细胞的定位和功能，对宿主防御微生物至关重要。
Enteric α-defensins, termed cryptdins (Crps) in mice, and lysozymes secreted by Paneth cells contribute to innate host defense in the ileum. Antimicrobial factors, including lysozymes and β-defensins, are often embedded in luminal glycosylated colonic Muc2 mucin secreted by goblet cells that form the protective mucus layer critical for gut homeostasis and pathogen invasion. In this study, we investigated ileal innate immunity against Entamoeba histolytica, the causative agent of intestinal amebiasis, by inoculating parasites in closed ileal loops inMuc2+/+andMuc2−/−littermates and quantifying Paneth cell localization (lysozyme expression) and function (Crp secretion). Relative toMuc2+/+littermates,Muc2−/−littermates showed a disorganized mislocalization of Paneth cells that was diffusely distributed, with elevated lysozyme secretion in the crypts and on villi in response to E. histolytica. Inhibition of E. histolytica Gal/GalNAc lectin (Gal-lectin) binding with exogenous galactose andEntamoeba histolyticacysteine proteinase 5 (EhCP5)-negative E. histolytica had no effect on parasite-induced erratic Paneth cell lysozyme synthesis. Although the basal ileal expression ofCrpgenes was unaffected inMuc2−/−mice in response to E. histolytica, there was a robust release of proinflammatory cytokines and Crp peptide secretions in luminal exudates that was also present in the colon. Interestingly, E. histolytica-secreted cysteine proteinases cleaved the proregion of Crp4 but not the active form. These findings define Muc2 mucin as an essential component of ileal barrier function that regulates the localization and function of Paneth cells critical for host defense against microbes.