Proteins produced by Streptococcus species in the lower respiratory tract can modify antiviral responses against influenza virus in respiratory epithelial cells

2020 ◽  
Author(s):  
Keisuke Nishioka ◽  
Michihito Kyo ◽  
Takaaki Nakaya ◽  
Nobuaki Shime
Keyword(s):  
Influenza Virus ◽  
Epithelial Cells ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Epithelial Cells ◽  
Antiviral Responses ◽  
Streptococcus Species ◽  
Respiratory Epithelial

scholarly journals Primary differentiated respiratory epithelial cells respond to apical measles virus infection by shedding multinucleated giant cells

2021 ◽  
Vol 118 (11) ◽  
pp. e2013264118
Author(s):  
Wen-Hsuan W. Lin ◽  
Annie J. Tsay ◽  
Erin N. Lalime ◽  
Andrew Pekosz ◽  
Diane E. Griffin
Keyword(s):  
Epithelial Cells ◽  
Respiratory Tract ◽  
Measles Virus ◽  
Giant Cells ◽  
Childhood Mortality ◽  
Apical Surface ◽  
Respiratory Epithelial Cells ◽  
Systemic Spread ◽  
Large Clusters ◽  
Respiratory Epithelial

Measles virus (MeV) is highly infectious by the respiratory route and remains an important cause of childhood mortality. However, the process by which MeV infection is efficiently established in the respiratory tract is controversial with suggestions that respiratory epithelial cells are not susceptible to infection from the apical mucosal surface. Therefore, it has been hypothesized that infection is initiated in lung macrophages or dendritic cells and that epithelial infection is subsequently established through the basolateral surface by infected lymphocytes. To better understand the process of respiratory tract initiation of MeV infection, primary differentiated respiratory epithelial cell cultures were established from rhesus macaque tracheal and nasal tissues. Infection of these cultures with MeV from the apical surface was more efficient than from the basolateral surface with shedding of viable MeV-producing multinucleated giant cell (MGC) syncytia from the surface. Despite presence of MGCs and infectious virus in supernatant fluids after apical infection, infected cells were not detected in the adherent epithelial sheet and transepithelial electrical resistance was maintained. After infection from the basolateral surface, epithelial damage and large clusters of MeV-positive cells were observed. Treatment with fusion inhibitory peptides showed that MeV production after apical infection was not dependent on infection of the basolateral surface. These results are consistent with the hypothesis that MeV infection is initiated by apical infection of respiratory epithelial cells with subsequent infection of lymphoid tissue and systemic spread.

scholarly journals Primary Swine Respiratory Epithelial Cell Lines for the Efficient Isolation and Propagation of Influenza A Viruses

2020 ◽  
Vol 94 (24) ◽  
Author(s):  
Victoria Meliopoulos ◽  
Sean Cherry ◽  
Nicholas Wohlgemuth ◽  
Rebekah Honce ◽  
Karen Barnard ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Epithelial Cells ◽  
Cell Lines ◽  
Influenza A ◽  
Vaccine Development ◽  
Mdck Cells ◽  
Influenza Viruses ◽  
Clinical Samples ◽  
Respiratory Epithelial Cells ◽  
Respiratory Epithelial

ABSTRACT Influenza virus isolation from clinical samples is critical for the identification and characterization of circulating and emerging viruses. Yet efficient isolation can be difficult. In these studies, we isolated primary swine nasal and tracheal respiratory epithelial cells and immortalized swine nasal epithelial cells (siNEC) and tracheal epithelial cells (siTEC) that retained the abilities to form tight junctions and cilia and to differentiate at the air-liquid interface like primary cells. Critically, both human and swine influenza viruses replicated in the immortalized cells, which generally yielded higher-titer viral isolates from human and swine nasal swabs, supported the replication of isolates that failed to grow in Madin-Darby canine kidney (MDCK) cells, and resulted in fewer dominating mutations during viral passaging than MDCK cells. IMPORTANCE Robust in vitro culture systems for influenza virus are critically needed. MDCK cells, the most widely used cell line for influenza isolation and propagation, do not adequately model the respiratory tract. Therefore, many clinical isolates, both animal and human, are unable to be isolated and characterized, limiting our understanding of currently circulating influenza viruses. We have developed immortalized swine respiratory epithelial cells that retain the ability to differentiate and can support influenza replication and isolation. These cell lines can be used as additional tools to enhance influenza research and vaccine development.

scholarly journals All-trans retinoic acid mediates DUOX2 expression and function in respiratory tract epithelium

2010 ◽  
Vol 299 (2) ◽  
pp. L215-L221 ◽  
Author(s):  
Angela Lee Linderholm ◽  
June Onitsuka ◽  
Changhong Xu ◽  
Maggie Chiu ◽  
Wai-Ming Lee ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Epithelial Cells ◽  
Respiratory Tract ◽  
Fold Increase ◽  
Respiratory Epithelial Cells ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Mrna And Protein Expression ◽  
And Function ◽  
Respiratory Epithelial

DUOX1 and DUOX2 are members of the NADPH oxidase family that are specifically regulated to produce hydrogen peroxide in epithelia of the thyroid, gastrointestinal tract, and respiratory tract. The determinants of DUOX1 or DUOX2 expression in various tissues have not been established. Using respiratory tract epithelial cells as a model, we investigated changes in DUOX mRNA and protein expression during the first 10 days of differentiation. By comparing a respiratory tract cell line, HBE1, with primary tracheobronchial epithelial (TBE) cells, we determined that DUOX2 was significantly expressed only in cell conditions that included all- trans retinoic acid (ATRA). In HBE1 cells, DUOX2 mRNA increased 6-fold after ATRA treatment. Similarly, ATRA induced a 19-fold increase in DUOX2 mRNA expression in primary TBE cells with parallel increases in DUOX protein and DUOX-mediated H2O2 production as well. In addition, DUOX2 induction by rhinovirus required the presence of ATRA. ATRA had no effect on DUOX1 expression for all the conditions studied. Our data indicate that for respiratory epithelial cells, ATRA is important in the regulation of DUOX2 expression, function, and rhinovirus-mediated DUOX2 inducibility.

scholarly journals Role of the Zinc Uptake ABC Transporter of Moraxella catarrhalis in Persistence in the Respiratory Tract

2013 ◽  
Vol 81 (9) ◽  
pp. 3406-3413 ◽  
Author(s):  
Timothy F. Murphy ◽  
Aimee L. Brauer ◽  
Charmaine Kirkham ◽  
Antoinette Johnson ◽  
Mary Koszelak-Rosenblum ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Respiratory Tract ◽  
Abc Transporter ◽  
Divalent Cations ◽  
Zinc Uptake ◽  
Wild Type ◽  
Human Respiratory Tract ◽  
Respiratory Epithelial Cells ◽  
Content Type ◽  
Respiratory Epithelial

ABSTRACTMoraxella catarrhalisis a human respiratory tract pathogen that causes otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease. We have identified and characterized a zinc uptake ABC transporter that is present in all strains ofM. catarrhalistested. A mutant in which theznugene cluster is knocked out shows markedly impaired growth compared to the wild type in medium that contains trace zinc; growth is restored to wild-type levels by supplementing medium with zinc but not with other divalent cations. Thermal-shift assays showed that the purified recombinant substrate binding protein ZnuA binds zinc but does not bind other divalent cations. Invasion assays with human respiratory epithelial cells demonstrated that the zinc ABC transporter ofM. catarrhalisis critical for invasion of respiratory epithelial cells, an observation that is especially relevant because an intracellular reservoir ofM. catarrhalisis present in the human respiratory tract and this reservoir is important for persistence. Theznuknockout mutant showed marked impairment in its capacity to persist in the respiratory tract compared to the wild type in a mouse pulmonary clearance model. We conclude that the zinc uptake ABC transporter mediates uptake of zinc in environments with very low zinc concentrations and is critical for full virulence ofM. catarrhalisin the respiratory tract in facilitating intracellular invasion of epithelial cells and persistence in the respiratory tract.

scholarly journals Influenza virus NS1 protein mutations at position 171 impact innate interferon responses by respiratory epithelial cells

2017 ◽  
Vol 240 ◽  
pp. 81-86 ◽  
Author(s):  
Ewan P. Plant ◽  
Natalia A. Ilyushina ◽  
Faruk Sheikh ◽  
Raymond P. Donnelly ◽  
Zhiping Ye
Keyword(s):  
Influenza Virus ◽  
Epithelial Cells ◽  
Ns1 Protein ◽  
Respiratory Epithelial Cells ◽  
Protein Mutations ◽  
Respiratory Epithelial ◽  
Interferon Responses

scholarly journals Influenza A Virus Infection Triggers Pyroptosis and Apoptosis of Respiratory Epithelial Cells through the Type I Interferon Signaling Pathway in a Mutually Exclusive Manner

2018 ◽  
Vol 92 (14) ◽  
Author(s):  
SangJoon Lee ◽  
Mikako Hirohama ◽  
Masayuki Noguchi ◽  
Kyosuke Nagata ◽  
Atsushi Kawaguchi
Keyword(s):  
Cell Death ◽  
Influenza Virus ◽  
Epithelial Cells ◽  
Virus Infection ◽  
Signaling Pathway ◽  
Influenza Virus Infection ◽  
Type I ◽  
Respiratory Epithelial Cells ◽  
Respiratory Epithelial ◽  
Early Phases

ABSTRACT Respiratory epithelial cell death by influenza virus infection is responsible for the induction of inflammatory responses, but the exact cell death mechanism is not understood. Here we showed that influenza virus infection induces apoptosis and pyroptosis in normal or precancerous human bronchial epithelial cells. Apoptosis was induced only in malignant tumor cells infected with influenza virus. In human precancerous respiratory epithelial cells (PL16T), the number of apoptotic cells increased at early phases of infection, but pyroptotic cells were observed at late phases of infection. These findings suggest that apoptosis is induced at early phases of infection but the cell death pathway is shifted to pyroptosis at late phases of infection. We also found that the type I interferon (IFN)-mediated JAK-STAT signaling pathway promotes the switch from apoptosis to pyroptosis by inhibiting apoptosis possibly through the induced expression of the Bcl-xL anti-apoptotic gene. Further, the inhibition of JAK-STAT signaling repressed pyroptosis but enhanced apoptosis in infected PL16T cells. Collectively, we propose that type I IFN signaling pathway triggers pyroptosis but not apoptosis in the respiratory epithelial cells in a mutually exclusive manner to initiate proinflammatory responses against influenza virus infection. IMPORTANCE Respiratory epithelium functions as a sensor of infectious agents to initiate inflammatory responses along with cell death. However, the exact cell death mechanism responsible for inflammatory responses by influenza virus infection is still unclear. We showed that influenza virus infection induced apoptosis and pyroptosis in normal or precancerous human bronchial epithelial cells. Apoptosis was induced at early phases of infection, but the cell death pathway was shifted to pyroptosis at late phases of infection under the regulation of type I IFN signaling to promote proinflammatory cytokine production. Taken together, our results indicate that the type I IFN signaling pathway plays an important role to induce pyroptosis but represses apoptosis in the respiratory epithelial cells to initiate proinflammatory responses against influenza virus infection.

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