Contribution of Epithelial Apoptosis and Subepithelial Immune Responses in Campylobacter jejuni-Induced Barrier Disruption

被引:23
|
作者
Butkevych, Eduard [1 ]
de Sa, Fabia Daniela Lobo [1 ]
Nattramilarasu, Praveen Kumar [1 ]
Buecker, Roland [1 ]
机构
[1] Chatite Univ Med Berlin, Inst Clin Physiol Nutr Med, Div Gastroenterol Infectiol & Rheumatol, Med Dept, Berlin, Germany
来源
FRONTIERS IN MICROBIOLOGY | 2020年 / 11卷
关键词
apoptosis; caspase; epithelial barrier; tumor necrosis factor alpha; Campylobacter; epithelial cell; immune cell co-culture; tight junction; CYTOLETHAL DISTENDING TOXIN; NF-KAPPA-B; TNF-ALPHA; TIGHT JUNCTIONS; IFN-GAMMA; CELL-LINE; HT-29/B6; CYTOKINE; OCCLUDIN; DEFECTS;
D O I
10.3389/fmicb.2020.00344
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Campylobacter jejuni is a widespread zoonotic pathogen and the leading bacterial cause of foodborne gastroenteritis in humans. Previous infection studies showed disruption of intercellular contacts, induction of epithelial apoptosis, and immune activation, all three contributing to intestinal barrier dysfunction leading to diarrhea. The present study aims to determine the impact of subepithelial immune cells on intestinal barrier dysfunction during Campylobacter jejuni infection and the underlying pathological mechanisms. Infection was performed in a co-culture of confluent monolayers of the human colon cell line HT-29/B6-GR/MR and THP-1 immune cells. Twenty-two hours after infection, transepithelial electrical resistance (TER) was decreased by 58 +/- 6% compared to controls. The infection resulted in an increase in permeability for fluorescein (332 Da; 4.5-fold) and for FITC-dextran (4 kDa; 3.5-fold), respectively. In contrast, incubation of the co-culture with the pan-caspase inhibitor Q-VD-OPh during the infection resulted in a complete recovery of the decrease in TER and a normalization of flux values. Fluorescence microscopy showed apoptotic fragmentation in infected cell monolayers resulting in a 5-fold increase of the apoptotic ratio, accompanied by an increased caspase-3 cleavage and caspase-3/7 activity, which both were not present after Q-VD-OPh treatment. Western blot analysis revealed increased claudin-1 and claudin-2 protein expression. Inhibition of apoptosis induction did not normalize these tight junction changes. TNF alpha concentration was increased during the infection in the co-culture. In conclusion, Campylobacter jejuni infection and the consequent subepithelial immune activation cause intestinal barrier dysfunction mainly through caspase-3-dependent epithelial apoptosis. Concomitant tight junction changes were caspase-independent. Anti-apoptotic and immune-modulatory substances appear to be promising agents for treatment of campylobacteriosis.
引用
收藏
页数:14
相关论文
共 50 条
  • [31] Modified Pulsatilla decoction attenuates oxazolone-induced colitis in mice through suppression of inflammation and epithelial barrier disruption
    Wang, Xuewei
    Fan, Fugang
    Cao, Qin
    MOLECULAR MEDICINE REPORTS, 2016, 14 (02) : 1173 - 1179
  • [32] Bletilla striata polysaccharide has a protective effect on intestinal epithelial barrier disruption in TAA-induced cirrhotic rats
    Luo, Lei
    Zhou, Zhang
    Xue, Juan
    Wang, Yao
    Zhang, Juan
    Cai, Xin
    Liu, Yuqing
    Yang, Fan
    EXPERIMENTAL AND THERAPEUTIC MEDICINE, 2018, 16 (03) : 1715 - 1722
  • [33] Activation of the Epithelial-to-Mesenchymal Transition Factor Snail Mediated Acetaldehyde-Induced Intestinal Epithelial Barrier Disruption
    Elamin, Elhaseen
    Masclee, Ad
    Troost, Freddy
    Dekker, Jan
    Jonkers, Daisy
    ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 2014, 38 (02) : 344 - 353
  • [34] MiR-339 attenuates LPS-induced intestinal epithelial cells inflammatory responses and apoptosis by targeting TLR4
    Xie, Meiying
    Zhang, Lina
    Li, Luoye
    Fan, Minhuan
    Hou, Lianjie
    GENES & GENOMICS, 2020, 42 (09) : 1097 - 1105
  • [35] Oxidant-induced disruption of intestinal epithelial barrier function: role of protein tyrosine phosphorylation
    Rao, RK
    Baker, RD
    Baker, SS
    Gupta, A
    Holycross, M
    AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 1997, 273 (04): : G812 - G823
  • [36] Rebamipide increases barrier function and attenuates TNFα-induced barrier disruption and cytokine expression in human corneal epithelial cells
    Tanaka, Hiroshi
    Fukuda, Ken
    Ishida, Waka
    Harada, Yosuke
    Sumi, Tamaki
    Fukushima, Atsuki
    BRITISH JOURNAL OF OPHTHALMOLOGY, 2013, 97 (07) : 912 - 916
  • [37] Nucleolar disruption and apoptosis are distinct neuronal responses to etoposide-induced DNA damage
    Pietrzak, Maciej
    Smith, Scott C.
    Geralds, Justin T.
    Hagg, Theo
    Gomes, Cynthia
    Hetman, Michal
    JOURNAL OF NEUROCHEMISTRY, 2011, 117 (06) : 1033 - 1046
  • [38] Antibiotic-Induced Disruption of Gut Microbiota Alters Local Metabolomes and Immune Responses
    Sun, Lin
    Zhang, Xiaoyan
    Zhang, Yuxiao
    Zheng, Kai
    Xiang, Qiaoyan
    Chen, Ning
    Chen, Zhiyun
    Zhang, Nan
    Zhu, Junping
    He, Qiushui
    FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 2019, 9
  • [39] Vasoactive intestinal peptide prevents PKCε-induced intestinal epithelial barrier disruption during EPEC infection
    Morampudi, V.
    Conlin, V. S.
    Dalwadi, U.
    Wu, X.
    Marshall, K. C.
    Nguyen, C.
    Vallance, B. A.
    Jacobson, K.
    AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2015, 308 (05): : G389 - G402
  • [40] Pharmacological stimulation of G-protein coupled receptor 40 alleviates cytokine-induced epithelial barrier disruption in airway epithelial Calu-3 cells
    Moonwiriyakit, Aekkacha
    Koval, Michael
    Muanprasat, Chatchai
    INTERNATIONAL IMMUNOPHARMACOLOGY, 2019, 73 : 353 - 361