scholarly journals Interferon Lambda Upregulates IDO1 Expression in Respiratory Epithelial Cells After Influenza Virus Infection

2015 ◽  
Vol 35 (7) ◽  
pp. 554-562 ◽  
Author(s):  
Julie M. Fox ◽  
Jackelyn M. Crabtree ◽  
Leo K. Sage ◽  
S. Mark Tompkins ◽  
Ralph A. Tripp
Keyword(s):  
Influenza Virus ◽  
Epithelial Cells ◽  
Virus Infection ◽  
Influenza Virus Infection ◽  
Respiratory Epithelial Cells ◽  
Interferon Lambda ◽  
Ido1 Expression ◽  
Respiratory Epithelial

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.

scholarly journals The Interferon-Inducible Proteoglycan Testican-2/SPOCK2 Functions as a Protective Barrier against Virus Infection of Lung Epithelial Cells

2019 ◽  
Vol 93 (20) ◽  
Author(s):  
Narae Ahn ◽  
Woo-Jong Kim ◽  
Nari Kim ◽  
Han Wook Park ◽  
Seung-Woo Lee ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Epithelial Cells ◽  
Virus Infection ◽  
Heparan Sulfate ◽  
Cell Attachment ◽  
Core Protein ◽  
Influenza Virus Infection ◽  
Lung Epithelial Cells ◽  
Extracellular Compartment ◽  
Lung Epithelial

ABSTRACT Proteoglycans function not only as structural components of the extracellular compartment but also as regulators of various cellular events, including cell migration, inflammation, and infection. Many microbial pathogens utilize proteoglycans to facilitate adhesion and invasion into host cells. Here we report a secreted form of a novel heparan sulfate proteoglycan that functions against virus infection. The expression of SPOCK2/testican-2 was significantly induced in virus-infected lungs or in interferon (IFN)-treated alveolar lung epithelial cells. Overexpression from a SPOCK2 expression plasmid alone or the treatment of cells with recombinant SPOCK2 protein efficiently blocked influenza virus infection at the step of viral attachment to the host cell and entry. Moreover, mice treated with purified SPOCK2 were protected against virus infection. Sialylated glycans and heparan sulfate chains covalently attached to the SPOCK2 core protein were critical for its antiviral activity. Neuraminidase (NA) of influenza virus cleaves the sialylated moiety of SPOCK2, thereby blocking its binding to the virus. Our data suggest that IFN-induced SPOCK2 functions as a decoy receptor to bind and block influenza virus infection, thereby restricting entry of the infecting virus into neighboring cells. IMPORTANCE Here we report a novel proteoglycan protein, testican-2/SPOCK2, that prevents influenza virus infection. Testican-2/SPOCK2 is a complex type of secreted proteoglycan with heparan sulfate GAG chains attached to the core protein. SPOCK2 expression is induced upon virus infection or by interferons, and the protein is secreted to an extracellular compartment, where it acts directly to block virus-cell attachment and entry. Treatment with purified testican-2/SPOCK2 protein can efficiently block influenza virus infection in vitro and in vivo. We also identified the heparan sulfate moiety as a key regulatory module for this inhibitory effect. Based on its mode of action (cell attachment/entry blocker) and site of action (extracellular compartment), we propose testican-2/SPOCK2 as a potential antiviral agent that can efficiently control influenza virus infection.

scholarly journals Desialylation of airway epithelial cells during influenza virus infection enhances pneumococcal adhesion via galectin binding

2015 ◽  
Vol 65 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Mihai Nita-Lazar ◽  
Aditi Banerjee ◽  
Chiguang Feng ◽  
Mohammed N. Amin ◽  
Matthew B. Frieman ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Epithelial Cells ◽  
Virus Infection ◽  
Influenza Virus Infection ◽  
Airway Epithelial Cells ◽  
Airway Epithelial

scholarly journals Correction: Suppression of Interferon Lambda Signaling by SOCS-1 Results in Their Excessive Production during Influenza Virus Infection

2016 ◽  
Vol 12 (1) ◽  
pp. e1005402 ◽  
Author(s):  
Haitao Wei ◽  
Song Wang ◽  
Qinghuang Chen ◽  
Yuhai Chen ◽  
Xiaojuan Chi ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza Virus Infection ◽  
Interferon Lambda

Inhibitory effects of carbocisteine on type A seasonal influenza virus infection in human airway epithelial cells

2010 ◽  
Vol 299 (2) ◽  
pp. L160-L168 ◽  
Author(s):  
Mutsuo Yamaya ◽  
Hidekazu Nishimura ◽  
Kyoko Shinya ◽  
Yukimasa Hatachi ◽  
Takahiko Sasaki ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Epithelial Cells ◽  
Virus Infection ◽  
Seasonal Influenza ◽  
Influenza Virus Infection ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Human Influenza ◽  
Inhibitory Effects ◽  
Human Influenza Virus

Type A human seasonal influenza (FluA) virus infection causes exacerbations of bronchial asthma and chronic obstructive pulmonary disease (COPD). l-carbocisteine, a mucolytic agent, reduces the frequency of common colds and exacerbations in COPD. However, the inhibitory effects of l-carbocisteine on FluA virus infection are uncertain. We studied the effects of l-carbocisteine on FluA virus infection in airway epithelial cells. Human tracheal epithelial cells were pretreated with l-carbocisteine and infected with FluA virus (H3N2). Viral titers in supernatant fluids, RNA of FluA virus in the cells, and concentrations of proinflammatory cytokines in supernatant fluids, including IL-6, increased with time after infection. l-carbocisteine reduced viral titers in supernatant fluids, RNA of FluA virus in the cells, the susceptibility to FluA virus infection, and concentrations of cytokines induced by virus infection. The epithelial cells expressed sialic acid with an α2,6-linkage (SAα2,6Gal), a receptor for human influenza virus on the cells, and l-carbocisteine reduced the expression of SAα2,6Gal. l-carbocisteine reduced the number of acidic endosomes from which FluA viral RNA enters into the cytoplasm and reduced the fluorescence intensity from acidic endosomes. Furthermore, l-carbocisteine reduced NF-κB proteins including p50 and p65 in the nuclear extracts of the cells. These findings suggest that l-carbocisteine may inhibit FluA virus infection, partly through the reduced expression of the receptor for human influenza virus in the human airway epithelial cells via the inhibition of NF-κB and through increasing pH in endosomes. l-carbocisteine may reduce airway inflammation in influenza virus infection.

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