Campylobacter jejuni infection suppressed Cl− secretion induced by CFTR activation in T-84 cells

Negoro, Sachie; Shimohata, Takaaki; Hatayama, Syo; Sato, Yuri; Matsumoto, Makoto; Iba, Hitomi; Aihara, Mutsumi; Uebanso, Takashi; Hamada, Yoshiro; Nishikawa, Yoshikazu; Yamasaki, Shinji; Mawatari, Kazuaki; Takahashi, Akira

doi:10.1016/j.jiac.2014.07.007

Cited by 10 publications

(10 citation statements)

References 33 publications

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“…Here in our study, we verified that T. vaginalis infection significantly inhibited anion secretion elicited by the luminal administration of PGE 2 in rat vaginal epithelium. As the major channel mediating anion transport, the apically located CFTR was reportedly down-regulated after pathogenic infection in host epithelial cells [27,44,45]. Consistent with these observations, we showed that T. vaginalis infection triggered down-regulation of CFTR in primary cultured rat vaginal epithelial cells, which may probably be the cause of impaired anion secretion.…”

Section: Discussionsupporting

confidence: 86%

“…Recent studies have demonstrated the impairment of transepithelial Cl − transport after infection with pathogens including C. jejuni [27], T. gondii [28], and influenza virus [44]. Here in our study, we verified that T. vaginalis infection significantly inhibited anion secretion elicited by the luminal administration of PGE 2 in rat vaginal epithelium.…”

Section: Discussionsupporting

confidence: 83%

“…Trichomoniasis has been demonstrated to be associated with severe adverse reproductive outcomes, such as infertility and multiple pregnancy complications [24][25][26], whilst the underlying mechanisms remain largely unclear. Recent studies showed that infection with pathogens including Campylobacter jejuni [27] and Toxoplasma gondii [28] impaired the function of analysis, decision to publish, or preparation of the manuscript.…”

Section: Introductionmentioning

confidence: 99%

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Trichomonas vaginalis infection impairs anion secretion in vaginal epithelium

et al. 2021

PLoS Negl Trop Dis

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Trichomonas vaginalis is a common protozoan parasite, which causes trichomoniasis associated with severe adverse reproductive outcomes. However, the underlying pathogenesis has not been fully understood. As the first line of defense against invading pathogens, the vaginal epithelial cells are highly responsive to environmental stimuli and contribute to the formation of the optimal luminal fluid microenvironment. The cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel widely distributed at the apical membrane of epithelial cells, plays a crucial role in mediating the secretion of Cl− and HCO3−. In this study, we investigated the effect of T. vaginalis on vaginal epithelial ion transport elicited by prostaglandin E2 (PGE2), a major prostaglandin in the semen. Luminal administration of PGE2 triggered a remarkable and sustained increase of short-circuit current (ISC) in rat vaginal epithelium, which was mainly due to Cl− and HCO3− secretion mediated by the cAMP-activated CFTR. However, T. vaginalis infection significantly abrogated the ISC response evoked by PGE2, indicating impaired transepithelial anion transport via CFTR. Using a primary cell culture system of rat vaginal epithelium and a human vaginal epithelial cell line, we demonstrated that the expression of CFTR was significantly down-regulated after T. vaginalis infection. In addition, defective Cl− transport function of CFTR was observed in T. vaginalis-infected cells by measuring intracellular Cl− signals. Conclusively, T. vaginalis restrained exogenous PGE2-induced anion secretion through down-regulation of CFTR in vaginal epithelium. These results provide novel insights into the intervention of reproductive complications associated with T. vaginalis infection such as infertility and disequilibrium in vaginal fluid microenvironment.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

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Trichomonas vaginalis infection impairs anion secretion in vaginal epithelium

et al. 2021

PLoS Negl Trop Dis

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“…A recent study showed that C. jejuni can affect Cl À secretion in T84 cells. 15 In our study, colon biopsies were tested in the Ussing chamber experiments after stimulation of electrogenic Cl À secretion either with PGE 2 and theophylline (by cAMPdependent activation) or with the cholinergic agonist carbachol ( Table 1). We found that the maximum transport rate during Figure 1 Electrogenic sodium transport in campylobacteriosis.…”

Section: Unchanged Epithelial Anion Secretion In C Jejuni-infected Cmentioning

confidence: 99%

Campylobacter jejuni impairs sodium transport and epithelial barrier function via cytokine release in human colon

et al. 2018

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Campylobacter jejuni is the most prevalent cause of foodborne bacterial enteritis worldwide. Patients present with diarrhea and immune responses lead to complications like arthritis and irritable bowel syndrome. Although studies exist in animal and cell models, we aimed at a functional and structural characterization of intestinal dysfunction and the involved regulatory mechanisms in human colon. First, in patients' colonic biopsies, sodium malabsorption was identified as an important diarrheal mechanism resulting from hampered epithelial ion transport via impaired epithelial sodium channel (ENaC) β- and γ-subunit. In addition, barrier dysfunction from disrupted epithelial tight junction proteins (claudin-1, -3, -4, -5, and -8), epithelial apoptosis, and appearance of lesions was detected, which cause leak-flux diarrhea and can perpetuate immune responses. Importantly, these effects in human biopsies either represent direct action of Campylobacter jejuni (ENaC impairment) or are caused by proinflammatory signaling (barrier dysfunction). This was revealed by regulator analysis from RNA-sequencing (cytometric bead array-checked) and confirmed in cell models, which identified interferon-γ, TNFα, IL-13, and IL-1β. Finally, bioinformatics' predictions yielded additional information on protective influences like vitamin D, which was confirmed in cell models. Thus, these are candidates for intervention strategies against C. jejuni infection and post-infectious sequelae, which result from the permissive barrier defect along the leaky gut.

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“…However, we previously reported that C. jejuni infection suppresses CFTR-mediated Cl Ϫ secretion in intestinal cells (20), which is a state opposite that associated with the clinical symptoms of C. jejuni infection, such as diarrhea. Thus, the relationship between CFTR suppression and C. jejuni infection is unclear.…”

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confidence: 90%

Cystic Fibrosis Transmembrane Conductance Regulator Reduces Microtubule-Dependent Campylobacter jejuni Invasion

et al. 2017

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Campylobacter jejuni is a foodborne pathogen that induces gastroenteritis. Invasion and adhesion are essential in the process of C. jejuni infection leading to gastroenteritis. The mucosal layer plays a key role in the system of defense against efficient invasion and adhesion by bacteria, which is modulated by several ion channels and transporters mediated by water flux in the intestine. The cystic fibrosis transmembrane conductance regulator (CFTR) plays the main role in water flux in the intestine, and it is closely associated with bacterial clearance. We previously reported that C. jejuni infection suppresses CFTR channel activity in intestinal epithelial cells; however, the mechanism and importance of this suppression are unclear. This study sought to elucidate the role of CFTR in C. jejuni infection. Using HEK293 cells that stably express wild-type and mutated CFTR, we found that CFTR attenuated C. jejuni invasion and that it was not involved in bacterial adhesion or intracellular survival but was associated with microtubule-dependent intracellular transport. Moreover, we revealed that CFTR attenuated the function of the microtubule motor protein, which caused inhibition of C. jejuni invasion, but did not affect microtubule stability. Meanwhile, the CFTR mutant G551D-CFTR, which had defects in channel activity, suppressed C. jejuni invasion, whereas the ΔF508-CFTR mutant, which had defects in maturation, did not suppress C. jejuni invasion, suggesting that CFTR suppression of C. jejuni invasion is related to CFTR maturation but not channel activity. When these findings are taken together, it may be seen that mature CFTR inhibits C. jejuni invasion by regulating microtubule-mediated pathways. We suggest that CFTR plays a critical role in cellular defenses against C. jejuni invasion and that suppression of CFTR may be an initial step in promoting cell invasion during C. jejuni infection.

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Campylobacter jejuni infection suppressed Cl− secretion induced by CFTR activation in T-84 cells

Cited by 10 publications

References 33 publications

Trichomonas vaginalis infection impairs anion secretion in vaginal epithelium

Trichomonas vaginalis infection impairs anion secretion in vaginal epithelium

Campylobacter jejuni impairs sodium transport and epithelial barrier function via cytokine release in human colon

Cystic Fibrosis Transmembrane Conductance Regulator Reduces Microtubule-Dependent Campylobacter jejuni Invasion

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