scholarly journals Role of Pht Proteins in Attachment of Streptococcus pneumoniae to Respiratory Epithelial Cells

2014 ◽  
Vol 82 (4) ◽  
pp. 1683-1691 ◽  
Author(s):  
Anna Kallio ◽  
Kirsi Sepponen ◽  
Philippe Hermand ◽  
Philippe Denoël ◽  
Fabrice Godfroid ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bacterial Attachment ◽  
Surface Proteins ◽  
Lung Epithelial Cells ◽  
Host Cells ◽  
Respiratory Epithelial Cells ◽  
Relative Significance ◽  
Mucosal Surfaces ◽  
Respiratory Epithelial

ABSTRACTPneumococcal adherence to mucosal surfaces is a critical step in nasopharyngeal colonization, but so far few pneumococcal adhesins involved in the interaction with host cells have been identified. PhtA, PhtB, PhtD, and PhtE are conserved pneumococcal surface proteins that have proven promising as vaccine candidates. One suggested virulence function of Pht proteins is to mediate adherence at the respiratory mucosa. In this study, we assessed the role of Pht proteins in pneumococcal binding to respiratory epithelial cells. Pneumococci were incubated with human nasopharyngeal epithelial cells (Detroit-562) and lung epithelial cells (A549 and NCI-H292), and the proportion of bound bacteria was measured by plating viable counts. Strains R36A (unencapsulated), D39 (serotype 2), 43 (serotype 3), 4-CDC (serotype 4), and 2737 (serotype 19F) with one or more of the four homologous Pht proteins deleted were compared with their wild-type counterparts. Also, the effect of anti-PhtD antibodies on the adherence of strain 2737 to the respiratory epithelial cells was studied. Our results suggest that Pht proteins play a role in pneumococcal adhesion to the respiratory epithelium. We also found that antibody to PhtD is able to inhibit bacterial attachment to the cells, suggesting that antibodies against PhtD present at mucosal surfaces might protect from pneumococcal attachment and subsequent colonization. However, the relative significance of Pht proteins to the ability of pneumococci to bindin vitroto epithelial cells depends on the genetic background and the capsular serotype of the strain.

scholarly journals SARS-CoV-2 drives JAK1/2-dependent local complement hyperactivation

2021 ◽  
Vol 6 (58) ◽  
pp. eabg0833
Author(s):  
Bingyu Yan ◽  
Tilo Freiwald ◽  
Daniel Chauss ◽  
Luopin Wang ◽  
Erin West ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Clinical Manifestations ◽  
Lung Epithelial Cells ◽  
Complement Factor ◽  
Respiratory Epithelial Cells ◽  
Signature Genes ◽  
Wide Range ◽  
Lung Epithelial ◽  
Gene Transcripts ◽  
Respiratory Epithelial

Patients with coronavirus disease 2019 (COVID-19) present a wide range of acute clinical manifestations affecting the lungs, liver, kidneys and gut. Angiotensin converting enzyme (ACE) 2, the best-characterized entry receptor for the disease-causing virus SARS-CoV-2, is highly expressed in the aforementioned tissues. However, the pathways that underlie the disease are still poorly understood. Here, we unexpectedly found that the complement system was one of the intracellular pathways most highly induced by SARS-CoV-2 infection in lung epithelial cells. Infection of respiratory epithelial cells with SARS-CoV-2 generated activated complement component C3a and could be blocked by a cell-permeable inhibitor of complement factor B (CFBi), indicating the presence of an inducible cell-intrinsic C3 convertase in respiratory epithelial cells. Within cells of the bronchoalveolar lavage of patients, distinct signatures of complement activation in myeloid, lymphoid and epithelial cells tracked with disease severity. Genes induced by SARS-CoV-2 and the drugs that could normalize these genes both implicated the interferon-JAK1/2-STAT1 signaling system and NF-κB as the main drivers of their expression. Ruxolitinib, a JAK1/2 inhibitor, normalized interferon signature genes and all complement gene transcripts induced by SARS-CoV-2 in lung epithelial cell lines, but did not affect NF-κB-regulated genes. Ruxolitinib, alone or in combination with the antiviral remdesivir, inhibited C3a protein produced by infected cells. Together, we postulate that combination therapy with JAK inhibitors and drugs that normalize NF-κB-signaling could potentially have clinical application for severe COVID-19.

Inhibition of alveolarization and altered pulmonary mechanics in mice expressing GATA-6

2003 ◽  
Vol 285 (6) ◽  
pp. L1246-L1254 ◽  
Author(s):  
Cong Liu ◽  
Machiko Ikegami ◽  
Mildred T. Stahlman ◽  
Chitta R. Dey ◽  
Jeffrey A. Whitsett
Keyword(s):  
Epithelial Cells ◽  
Surfactant Protein ◽  
Mouse Lung ◽  
Pulmonary Mechanics ◽  
Respiratory Epithelial Cells ◽  
Surfactant Protein C ◽  
Spatial Regulation ◽  
Respiratory Epithelial ◽  
Tissue Elastance

GATA-6, a member of a family of zinc finger transcription factors, is expressed in epithelial cells of the developing lung. To further assess the role of GATA-6 in lung morphogenesis, GATA-6 was expressed in respiratory epithelial cells of the developing mouse lung under control of the surfactant protein C promoter (hSP-CGATA-6 mice). Although GATA-6 did not alter lung morphology at embryonic day 18.5, defects in alveolar septation were observed early in the neonatal period, and air space enlargement persisted to adulthood. Airway resistance, airway elastance, tissue damping, and tissue elastance were significantly decreased, and lung volumes were significantly increased at 12 wk of age. Normal postnatal morphogenesis of the lung depends upon precise temporal-spatial regulation of GATA-6.

Bioassay of a tracheal smooth muscle-constricting factor released by respiratory epithelial cells

1992 ◽  
Vol 263 (1) ◽  
pp. L137-L141 ◽  
Author(s):  
J. H. Wilkens ◽  
A. Becker ◽  
H. Wilkens ◽  
M. Emura ◽  
M. Riebe-Imre ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Muscle Tone ◽  
Lung Epithelial Cells ◽  
Epithelial Cell Line ◽  
Cell Column ◽  
Respiratory Epithelial Cells ◽  
Lung Epithelial ◽  
Respiratory Epithelial

Epithelium-derived factors of unknown identity have been proposed to modulate airway smooth muscle tone. We developed a novel sensitive bioassay system that allows serial perfusion of cultured respiratory epithelial cells and guinea pig trachea (GPT). GPT responses were assessed as diameter changes by computerized video microscopy (resolution, 15 microns). A permanent hamster lung epithelial cell line was grown on microcarrier beads and perfused in a cell column. When the outflow tubing from the epithelial cell column was connected to the inflow cannula, the detector GPT contracted, reaching 28 +/- 6% of the maximum methacholine (100 microM)-induced contraction (n = 12, P less than 0.001). Perfusion of the cell column with diclofenac (10 microM) or lysin-mono-acetylsalicylic acid (100 microM) abolished the GPT contraction, whereas selective perfusion of the detector GPT with either agent did not block the contraction. Analysis of the effluent of the epithelial cell column demonstrated a significant basal release of prostaglandins F2 alpha and E2 (PGF2 alpha and PGE2) and 6-ketoprostaglandin F1 alpha, whereas only marginal amounts of thromboxane B2 were detected. When given exogenously, PGF2 alpha, PGE2, PGI2, and U-46619 all contracted the GPT. It is concluded that lung epithelial cells can contract GPT by releasing a transferable factor. This factor is likely to be a constrictor cyclooxygenase product that is not produced in epithelium-denuded GPT.

scholarly journals A Role of Epithelial Cells and Virulence Factors in Biofilm Formation by Streptococcus pyogenes In Vitro

2020 ◽  
Vol 88 (10) ◽  
Author(s):  
Feiruz Alamiri ◽  
Yashuan Chao ◽  
Maria Baumgarten ◽  
Kristian Riesbeck ◽  
Anders P. Hakansson
Keyword(s):  
Antibiotic Resistance ◽  
Epithelial Cells ◽  
Virulence Factors ◽  
Streptococcus Pyogenes ◽  
Biofilm Formation ◽  
Model Systems ◽  
Respiratory Epithelial Cells ◽  
Abiotic Surfaces ◽  
Respiratory Epithelial

ABSTRACT Biofilm formation by Streptococcus pyogenes (group A streptococcus [GAS]) in model systems mimicking the respiratory tract is poorly documented. Most studies have been conducted on abiotic surfaces, which poorly represent human tissues. We have previously shown that GAS forms mature and antibiotic-resistant biofilms on physiologically relevant epithelial cells. However, the roles of the substratum, extracellular matrix (ECM) components, and GAS virulence factors in biofilm formation and structure are unclear. In this study, biofilm formation was measured on respiratory epithelial cells and keratinocytes by determining biomass and antibiotic resistance, and biofilm morphology was visualized using scanning electron microscopy. All GAS isolates tested formed biofilms that had similar, albeit not identical, biomass and antibiotic resistance for both cell types. Interestingly, functionally mature biofilms formed more rapidly on keratinocytes but were structurally denser and coated with more ECM on respiratory epithelial cells. The ECM was crucial for biofilm integrity, as protein- and DNA-degrading enzymes induced bacterial release from biofilms. Abiotic surfaces supported biofilm formation, but these biofilms were structurally less dense and organized. No major role for M protein, capsule, or streptolysin O was observed in biofilm formation on epithelial cells, although some morphological differences were detected. NAD-glycohydrolase was required for optimal biofilm formation, whereas streptolysin S and cysteine protease SpeB impaired this process. Finally, no correlation was found between cell adherence or autoaggregation and GAS biofilm formation. Combined, these results provide a better understanding of the role of biofilm formation in GAS pathogenesis and can potentially provide novel targets for future treatments against GAS infections.

scholarly journals Effect of calcium on the interaction of Acinetobacter baumannii with human respiratory epithelial cells

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yi Chen ◽  
Tingjun Shao ◽  
Sanhua Fang ◽  
Ping Pan ◽  
Jiahui Jiang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Acinetobacter Baumannii ◽  
Host Cells ◽  
Effective Control ◽  
Respiratory Epithelial Cells ◽  
Cellular Analysis ◽  
Bacterial Interaction ◽  
Dependent Cell ◽  
Human Respiratory Epithelial Cells ◽  
Respiratory Epithelial

Abstract Background Investigating the factors that influence Acinetobacter baumannii(Ab) adhesion/invasion of host cells is important to understand its pathogenicity. Metal cations have been shown to play an important role in regulating the biofilm formation and increasing the virulence of Ab; however, the effect of calcium on host-bacterial interaction has yet to be clarified. Here, the dynamic process of the interaction between Ab and human respiratory epithelial cells and the effect of calcium on host-bacterial interaction were explored using microscopic imaging, quantitative PCR and real time cellular analysis (RTCA). Results The concentration of calcium, multiplicity of infection and co-culture time were all demonstrated to have effects on host-bacterial interaction. A unique “double peak” phenomenon changed to a sharp “single peak” phenomenon during the process of Ab infection under the effect of calcium was observed in the time-dependent cell response profiles. Moreover, calcium can increase Ab adhesion/invasion of epithelial cells by regulating the expression of Ab-related genes (ompA, bfmRS, abaI). Conclusions Effective control of calcium concentrations can provide new approaches for the prevention and treatment of multi-drug resistant Ab.

scholarly journals Differential Role of CbpA and PspA in Modulation of In Vitro CXC Chemokine Responses of Respiratory Epithelial Cells to Infection with Streptococcus pneumoniae

2006 ◽  
Vol 74 (12) ◽  
pp. 6739-6749 ◽  
Author(s):  
Rikki M. A. Graham ◽  
James C. Paton
Keyword(s):  
Streptococcus Pneumoniae ◽  
Epithelial Cells ◽  
Deletion Mutant ◽  
Protein A ◽  
A549 Cells ◽  
Respiratory Pathogens ◽  
Respiratory Epithelial Cells ◽  
Cxc Chemokine ◽  
Respiratory Epithelial

ABSTRACTRespiratory epithelial cells play an active part in the host response to respiratory pathogens, such asStreptococcus pneumoniae, by releasing chemokines responsible for neutrophil recruitment. In order to investigate the role of specific pneumococcal virulence factors in eliciting CXC chemokine responses, type II pneumocytes (A549) and nasopharyngeal cells (Detroit-562) were infected withS. pneumoniaeD39 or mutants lacking choline-binding protein A (CbpA), pneumococcal surface protein A (PspA), or specific domains thereof. In response to wild-type D39, both A549 and Detroit-562 cells showed a significant increase in CXC chemokine mRNA and interleukin-8 protein. This response was increased twofold when acbpAdeletion mutant (ΔCbpA) was used, suggesting that CbpA inhibits CXC chemokine induction. All three N-terminal domains of CbpA are required for this effect, as in-frame deletion of the respective region ofcbpAhad the same effect on the CXC chemokine response as deletion ofcbpAaltogether. Infection with apspAdeletion mutant (ΔPspA) led to a twofold decrease in the CXC chemokine response of A549 but not Detroit-562 cells, compared to infection with D39 at 2 h. Thus, PspA appears to have the ability to stimulate early CXC chemokine release from A549 cells. Deletion of the region ofpspAencoding the first N-terminal α-helical domain reduced the ability ofS. pneumoniaeto elicit a chemokine response to the same degree as deletion ofpspAaltogether. Thus, the N termini of CbpA and PspA exert differential effects on CXC chemokine induction in epithelial cells infected withS. pneumoniae.

Zinc chelators inhibit eotaxin, RANTES, and MCP-1 production in stimulated human airway epithelium and fibroblasts

2003 ◽  
Vol 285 (3) ◽  
pp. L719-L729 ◽  
Author(s):  
Martin Richter ◽  
André M. Cantin ◽  
Claudia Beaulieu ◽  
Alexandre Cloutier ◽  
Pierre Larivée
Keyword(s):  
Epithelial Cells ◽  
Airway Epithelium ◽  
Rnase Protection Assay ◽  
Zinc Content ◽  
Lung Epithelial Cells ◽  
Respiratory Epithelial Cells ◽  
Rnase Protection ◽  
Human Airway Epithelium ◽  
Zinc Chelator ◽  
Respiratory Epithelial

Asthma is characterized by an increased production of eosinophil-active C-C chemokines by the airway epithelium. Recent studies have identified the presence of important quantities of labile zinc in the conducting airways. We hypothesized that modulation of this labile zinc could influence the production of proinflammatory chemokines in respiratory epithelial cells. The zinc chelator N,N,N′ ,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) and the heavy metal chelator 2,3-dimercapto-1-propanesulfonic acid (DMPS) were used to reduce the labile zinc content of A549, BEAS-2B, and HFL-1 cells. Northern blot analysis and RNase protection assay were used to study the effects of the zinc chelators on mRNA expression. DMPS and TPEN specifically inhibited the production of eotaxin, regulated on activation, normal T-cell expressed, and presumably secreted, and monocyte chemotactic protein-1 in TNF-α-stimulated respiratory epithelial cells and fibroblasts through labile zinc chelation. The inhibitory effects of DMPS and TPEN were associated with the decreased binding of the zinc-finger transcription factor GATA-1, whereas no change in NF-κB activation was observed. Together these results demonstrate that modulation of the labile pool of zinc can regulate gene expression and protein synthesis of C-C chemokines in lung epithelial cells and fibroblasts.

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