A model of the deciliation process caused by Mycoplasma fermentans strain incognitus on respiratory epithelium

Stadtländer, Christian T. K.-H.

doi:10.1002/sca.4950280403

Cited by 5 publications

(3 citation statements)

References 27 publications

(33 reference statements)

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“…Explants have been successfully assessed to study the pathogenesis of viral respiratory diseases [ 23 , 29 – 31 ] and, less frequently, of respiratory mycoplasmosis in both humans and animals [ 32 – 35 ]. Taken together, data reported herein confirm that explants can be easily obtained from slaughtered cattle [ 29 ] and indicate that BREs—particularly lung explants—provide the adequate microenvironment for Mmm survival and growth, closely resembling the in vivo habitat of this pathogen.…”

Section: Discussionmentioning

confidence: 99%

Respiratory explants as a model to investigate early events of contagious bovine pleuropneumonia infection

Teodoro

Marruchella

Provvido

et al. 2018

Vet Res

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Contagious bovine pleuropneumonia (CBPP) is a severe disease caused by Mycoplasma mycoides subsp. mycoides (Mmm). Knowledge on CBPP pathogenesis is fragmented and hampered by the limited availability of laboratory animal and in vitro models of investigation. The purpose of the present study is to assess respiratory explants as useful tools to study the early stages of CBPP. Explants were obtained from trachea, bronchi and lungs of slaughtered cattle, tested negative for Mycoplasma spp. and for the major bacterial and viral respiratory pathogens. The interaction of Mmm with explant cells was studied by immunohistochemistry (IHC), double-labelling indirect immunofluorescence (DLIIF) and laser scanning confocal microscopy (LSCM). Mmm capability to survive and proliferate within the explants was evaluated by standard microbiological procedures. Finally, the putative cellular internalization of Mmm was further investigated by the gentamicin invasion assay. IHC and DLIIF indicated that Mmm can colonize explants, showing a marked tropism for lower airways. Specifically, Mmm was detected on/inside the bronchiolar and alveolar epithelial cells, the alveolar macrophages and the endothelial cells. The interaction between Mmm and explant cells was abolished by the pre-incubation of the pathogen with bovine anti-Mmm immune sera. Mmm was able to survive and proliferate in all tracheal, bronchial and lung explants, during the entire time course of the experiments. LSCM and gentamicin invasion assay both confirmed that Mmm can enter non-phagocytic host cells. Taken together, our data supports bovine respiratory explants as a promising tool to investigate CBPP, alternative to cattle experimental infection.Electronic supplementary materialThe online version of this article (10.1186/s13567-017-0500-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Respiratory explants as a model to investigate early events of contagious bovine pleuropneumonia infection

Teodoro

Marruchella

Provvido

et al. 2018

Vet Res

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“…Indeed, kidney cells may be exposed to certain metabolites in the filtrate, such as ammonium ions, that have previously been shown to mediate the deciliating activity of pathogenic Ureaplasma infection of the oviduct (Stalheim and Gallagher, 1977). Mycoplasma infection of the upper respiratory tract also causes deciliation (Stadtlander, 2006), but the consequences of urinary tract infections on renal epithelial cilia have not been reported. Perhaps ciliary shedding provides a protective signal to the epithelium, informing cells to "hunker down" by tightening their junctions and regulating their endocytic and exocytic trafficking pathways.…”

Section: Discussionmentioning

confidence: 99%

Deciliation Is Associated with Dramatic Remodeling of Epithelial Cell Junctions and Surface Domains

Overgaard¹,

Sanzone²,

Spiczka³

et al. 2009

MBoC

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Stress-induced shedding of motile cilia (autotomy) has been documented in diverse organisms and likely represents a conserved cellular reaction. However, little is known about whether primary cilia are shed from mammalian epithelial cells and what impact deciliation has on polarized cellular organization. We show that several chemically distinct agents trigger autotomy in epithelial cells. Surprisingly, deciliation is associated with a significant, but reversible increase in transepithelial resistance. This reflects substantial reductions in tight junction proteins associated with "leaky" nephron segments (e.g., claudin-2). At the same time, apical trafficking of gp80/clusterin and gp114/CEACAM becomes randomized, basal-lateral delivery of Na,K-ATPase is reduced, and expression of the nonciliary apical protein gp135/podocalyxin is greatly decreased. However, ciliogenesis-impaired MDCK cells do not undergo continual junction remodeling, and mature cilia are not required for autotomy-associated remodeling events. Deciliation and epithelial remodeling may be mechanistically linked processes, because RNAi-mediated reduction of Exocyst subunit Sec6 inhibits ciliary shedding and specifically blocks deciliation-associated down-regulation of claudin-2 and gp135. We propose that ciliary autotomy represents a signaling pathway that impacts the organization and function of polarized epithelial cells.

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“…Mycoplasma infection of the upper respiratory tract also causes deciliation (Stadtlander 2006), but the consequences of urinary tract infections on renal epithelial cilia have not been reported. Perhaps ciliary shedding provides a protective signal to the epithelium, informing cells to "hunker down" by tightening their junctions and regulating their endocytic and exocytic trafficking pathways.…”

Section: Discussionmentioning

confidence: 99%

Deciliation dramatically alters epithelial function

Overgaard¹

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Primary cilia are sensory organelles present on most differentiated cells. Their assembly or function is impaired in several human diseases, including polycystic kidney disease (PKD). However, the mechanism by which ciliary dysfunction contributes to these pathologies is incompletely understood. PKD is characterized by altered transepithelial fluid transport, due to the mislocalization of ion pumps and changes in tight junctions. How ciliary dysregulation might lead to such changes in cell polarity and tight-junction function has not been shown. The overall hypothesis of this thesis is that ciliary dysfunction promotes specific changes in epithelial junctions and cell polarity that contribute to PKD. We developed an experimental model in which to test whether ciliary disruption indeed causes changes in cell polarity and tight junctions, and used it in conjunction with well-established methods to chemically induce ciliary shedding from cells, and with assays measuring the distribution of surface and secretory proteins in Madin-Darby canine kidney (MDCK) cells. This analysis revealed that several proteins, including Na/K-ATPase, were mislocalized following deciliation and that tight junctions became less permeable to paracellular ion flux. We infer that the combined effects of mislocalized ion transporters and increased tight-junction barrier function contribute to cyst formation in PKD. The functional specificity of tight junctions is determined by their expression of claudins, a protein family consisting of 24 members. Of these, claudin 2 expression has been shown to lead to an increase in junctional leakiness. We found that upon deciliation, claudin 2 expression was lost and trans-epithelial resistance increased 3-fold. The signaling pathway connecting deciliation to claudin 2 repression required ERK activation; phospho-ERK levels were elevated after exposure to deciliation stimuli, and an inhibitor of ERK activation blocked claudin 2 loss. The down-regulation of claudin 2 did not involve post-translational regulation, because protein half-life was not altered following deciliation. In contrast, the half-life of claudin 2 mRNA was ACKNOWLEDGMENTS I must begin by thanking my advisor, Dr. Chuck Yeaman. The years of support and tolerance have been a great help. Also, thank you to the other members of the Yeaman lab: Nick, Clay, and the inestimable Krystle for making the daily grind a little more bearable.

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A model of the deciliation process caused by Mycoplasma fermentans strain incognitus on respiratory epithelium

Cited by 5 publications

References 27 publications

Respiratory explants as a model to investigate early events of contagious bovine pleuropneumonia infection

Respiratory explants as a model to investigate early events of contagious bovine pleuropneumonia infection

Deciliation Is Associated with Dramatic Remodeling of Epithelial Cell Junctions and Surface Domains

Deciliation dramatically alters epithelial function

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