scholarly journals Bleomycin-Induced Lung Injury Increases Resistance to Influenza Virus Infection in a Type I Interferon-Dependent Manner

2021 ◽  
Vol 12 ◽  
Author(s):  
Sang-Uk Seo ◽  
Jae-Hyeon Jeong ◽  
Bum-Seo Baek ◽  
Je-Min Choi ◽  
Youn Soo Choi ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Lung Injury ◽  
Inflammatory Cytokine ◽  
Type I Interferon ◽  
Influenza Infection ◽  
Influenza Virus Infection ◽  
Type I ◽  
Dependent Manner ◽  
Infection Period

Acute lung injury (ALI) results in acute respiratory disease that causes fatal respiratory diseases; however, little is known about the incidence of influenza infection in ALI. Using a ALI-mouse model, we investigated the pro-inflammatory cytokine response to ALI and influenza infection. Mice treated with bleomycin (BLM), which induces ALI, were more resistant to influenza virus infection and exhibited higher levels of type I interferon (IFN-I) transcription during the early infection period than that in PBS-treated control mice. BLM-treated mice also exhibited a lower viral burden, reduced pro-inflammatory cytokine production, and neutrophil levels. In contrast, BLM-treated IFN-I receptor 1 (IFNAR1)-knockout mice failed to show this attenuated phenotype, indicating that IFN-I is key to the antiviral response in ALI-induced mice. The STING/TBK1/IRF3 pathway was found to be involved in IFN-I production and the establishment of an antiviral environment in the lung. The depletion of plasmacytoid dendritic cells (pDCs) reduced the effect of BLM treatment against influenza virus infection, suggesting that pDCs are the major source of IFN-I and are crucial for defense against viral infection in BLM-induced lung injury. Overall, this study showed that BLM-mediated ALI in mice induced the release of double-stranded DNA, which in turn potentiated IFN-I-dependent pulmonary viral resistance by activating the STING/TBK1/IRF3 pathway in association with pDCs.

Obesity worsens the outcome of influenza virus infection associated with impaired type I interferon induction in mice

2019 ◽  
Vol 513 (2) ◽  
pp. 405-411 ◽  
Author(s):  
Ho Namkoong ◽  
Makoto Ishii ◽  
Hideki Fujii ◽  
Takahiro Asami ◽  
Kazuma Yagi ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Type I Interferon ◽  
Influenza Virus Infection ◽  
Type I ◽  
Interferon Induction

scholarly journals Influenza Virus Infection Enhances Antibody-Mediated NK Cell Functions via Type I Interferon-Dependent Pathways

2018 ◽  
Vol 93 (5) ◽  
Author(s):  
Sinthujan Jegaskanda ◽  
Hillary A. Vanderven ◽  
Hyon-Xhi Tan ◽  
Sheilajen Alcantara ◽  
Kathleen M. Wragg ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Nk Cells ◽  
Nk Cell ◽  
Type I Interferon ◽  
A549 Cells ◽  
Influenza Virus Infection ◽  
Type I ◽  
Cell Functions ◽  
Infected Cells

ABSTRACT Natural killer (NK) cells are an important component in the control of influenza virus infection, acting to both clear virus-infected cells and release antiviral cytokines. Engagement of CD16 on NK cells by antibody-coated influenza virus-infected cells results in antibody-dependent cellular cytotoxicity (ADCC). Increasing the potency of antibody-mediated NK cell activity could ultimately lead to improved control of influenza virus infection. To understand if NK cells can be functionally enhanced following exposure to influenza virus-infected cells, we cocultured human peripheral blood mononuclear cells (PBMCs) with influenza virus-infected human alveolar epithelial (A549) cells and evaluated the capacity of NK cells to mediate antibody-dependent functions. Preincubation of PBMCs with influenza virus-infected cells markedly enhanced the ability of NK cells to respond to immune complexes containing hemagglutinin (HA) and anti-HA antibodies or transformed allogeneic cells in the presence or absence of a therapeutic monoclonal antibody. Cytokine multiplex, RNA sequencing, supernatant transfer, Transwell, and cytokine-blocking/cytokine supplementation experiments showed that type I interferons released from PBMCs were primarily responsible for the influenza virus-induced enhancement of antibody-mediated NK cell functions. Importantly, the influenza virus-mediated increase in antibody-dependent NK cell functionality was mimicked by the type I interferon agonist poly(I·C). We conclude that the type I interferon secretion induced by influenza virus infection enhances the capacity of NK cells to mediate ADCC and that this pathway could be manipulated to alter the potency of anti-influenza virus therapies and vaccines. IMPORTANCE Protection from severe influenza may be assisted by antibodies that engage NK cells to kill infected cells through ADCC. Studies have primarily focused on antibodies that have ADCC activity, rather than the capacity of NK cells to become activated and mediate ADCC during an influenza virus infection. We found that type I interferon released in response to influenza virus infection primes NK cells to become highly reactive to anti-influenza virus ADCC antibodies. Enhancing the capacity of NK cells to mediate ADCC could assist in controlling influenza virus infections.

scholarly journals The Role of Interferon in Influenza Virus Tissue Tropism

1998 ◽  
Vol 72 (11) ◽  
pp. 8550-8558 ◽  
Author(s):  
Adolfo García-Sastre ◽  
Russell K. Durbin ◽  
Hongyong Zheng ◽  
Peter Palese ◽  
Rachel Gertner ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Cell Lines ◽  
Virus Replication ◽  
Influenza A ◽  
Type I Interferon ◽  
Influenza Virus Infection ◽  
Fibroblast Cell ◽  
Type I ◽  
Fibroblast Cell Lines

ABSTRACT We have studied the pathogenesis of influenza virus infection in mice that are unable to respond to type I or II interferons due to a targeted disruption of the STAT1 gene. STAT1−/− animals are 100-fold more sensitive to lethal infection with influenza A/WSN/33 virus than are their wild-type (WT) counterparts. Virus replicated only in the lungs of WT animals following intranasal (i.n.) virus inoculation, while STAT1−/− mice developed a fulminant systemic influenza virus infection following either i.n. or intraperitoneal inoculation. We investigated the mechanism underlying this altered virus tropism by comparing levels of virus replication in fibroblast cell lines and murine embryonic fibroblasts derived from WT mice, STAT−/− mice, and mice lacking gamma interferon (IFNγ−/− mice) or the IFN-α receptor (IFNαR−/− mice). Influenza A/WSN/33 virus replicates to high titers in STAT1−/− or IFNαR−/− fibroblasts, while cells derived from WT or IFNγ−/− animals are resistant to influenza virus infection. Immunofluorescence studies using WT fibroblast cell lines demonstrated that only a small subpopulation of WT cells can be infected and that in the few infected WT cells, virus replication is aborted at an early, nuclear phase. In all organs examined except the lung, influenza A WSN/33 virus infection is apparently prevented by an intact type I interferon response. Our results demonstrate that type I interferon plays an important role in determining the pathogenicity and tissue restriction of influenza A/WSN/33 virus in vivo and in vitro.

scholarly journals Low basal expression and slow induction of IFITM3 puts immune cells at risk of influenza A infection

2019 ◽  
Author(s):  
Dannielle Wellington ◽  
Zixi Yin ◽  
Liwei Zhang ◽  
Jessica Forbester ◽  
Kerry Kite ◽  
...  
Keyword(s):  
At Risk ◽  
Influenza Virus ◽  
Virus Infection ◽  
Viral Infection ◽  
Immune Cells ◽  
Transmembrane Protein ◽  
Influenza Infection ◽  
Influenza Virus Infection ◽  
Type I ◽  
Basal Expression

AbstractThe interferon-induced transmembrane protein, IFITM3, has been shown to restrict influenza virus infection in murine and in vitro settings for ten years, but no explanation has been found to explain why this virus infection is so highly contagious and infects most individuals it comes in contact with. We confirm that the expression level of IFITM3 plays a role in determining the level of viral infection through manipulation of IFITM3 levels with interferon (IFN) stimulation and overexpression systems. Low basal expression may put some immune cells, including lymphocytes and lung-resident macrophages, at risk of influenza virus infection. Investigating the induction of IFITM3 by IFN, we find a strong preference for Type I IFN in IFITM3 induction in both cell lines and primary human cells. While myeloid cells can increase expression following stimulation by Type I IFN, lymphocytes show minimal induction of IFITM3 following IFN stimulation, suggesting that they are always at risk of viral infection. Surprisingly, we found that the time it takes for maximal induction of IFITM3 is relatively slow for an interferon-stimulated gene at around 36 hours. Low basal expression and slow induction of IFITM3 could increase the risk of influenza virus infection in selected immune cells.ImportanceInfluenza virus infection remains one of the top ten threats to global health, causing significant deaths and hospitalisations across the world each year. Understanding mechanisms for controlling influenza virus infection remain a priority. The interferon-induced transmembrane protein IFITM3 can restrict influenza infection by limiting replication of the virus. The precise mechanisms of how IFITM3 reduced replication of influenza are unknown, although it is predicted to prevent release of viral contents into the cytosol by preventing pore formation on the endosomal compartments where it is suggested to reside. Here we have shown that the expression level of IFITM3 is important in determining the control of influenza virus infection. We find an expression pattern for IFITM3 that varies based on cell type, tissue locality, differentiation state and cell naivety, all of which highlights cells that may be at the highest risk of influenza infection.

scholarly journals Type I Interferon Imposes a TSG101/ISG15 Checkpoint at the Golgi for Glycoprotein Trafficking during Influenza Virus Infection

2013 ◽  
Vol 14 (5) ◽  
pp. 510-521 ◽  
Author(s):  
Sumana Sanyal ◽  
Joseph Ashour ◽  
Takeshi Maruyama ◽  
Arwen F. Altenburg ◽  
Juan Jose Cragnolini ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Type I Interferon ◽  
Influenza Virus Infection ◽  
Type I

scholarly journals Performance of case definitions and clinical predictors for influenza surveillance among patients followed in a rural cohort in Senegal

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mamadou Aliou Barry ◽  
Florent Arinal ◽  
Cheikh Talla ◽  
Boris Gildas Hedible ◽  
Fatoumata Diene Sarr ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Sore Throat ◽  
Predictive Value ◽  
Influenza Infection ◽  
Clinical Signs ◽  
Influenza Virus Infection ◽  
Nasal Discharge ◽  
Age Group ◽  
Case Definitions

Abstract Background Influenza is a major cause of morbidity and mortality in Africa. However, a lack of epidemiological data remains for this pathology, and the performances of the influenza-like illness (ILI) case definitions used for sentinel surveillance have never been evaluated in Senegal. This study aimed to i) assess the performance of three different ILI case definitions, adopted by the WHO, USA-CDC (CDC) and European-CDC (ECDC) and ii) identify clinical factors associated with a positive diagnosis for Influenza in order to develop an algorithm fitted for the Senegalese context. Methods All 657 patients with a febrile pathological episode (FPE) between January 2013 and December 2016 were followed in a cohort study in two rural villages in Senegal, accounting for 1653 FPE observations with nasopharyngeal sampling and influenza virus screening by rRT-PCR. For each FPE, general characteristics and clinical signs presented by patients were collected. Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for the three ILI case definitions were assessed using PCR result as the reference test. Associations between clinical signs and influenza infection were analyzed using logistic regression with generalized estimating equations. Sore throat, arthralgia or myalgia were missing for children under 5 years. Results WHO, CDC and ECDC case definitions had similar sensitivity (81.0%; 95%CI: 77.0–85.0) and NPV (91.0%; 95%CI: 89.0–93.1) while the WHO and CDC ILI case definitions had the highest specificity (52.0%; 95%CI: 49.1–54.5) and PPV (32.0%; 95%CI: 30.0–35.0). These performances varied by age groups. In children < 5 years, the significant predictors of influenza virus infection were cough and nasal discharge. In patients from 5 years, cough, nasal discharge, sore throat and asthenia grade 3 best predicted influenza infection. The addition of “nasal discharge” as a symptom to the WHO case definition decreased sensitivity but increased specificity, particularly in the pediatric population. Conclusion In summary, all three definitions studies (WHO, ECDC & CDC) have similar performance, even by age group. The revised WHO ILI definition could be chosen for surveillance purposes for its simplicity. Symptomatic predictors of influenza virus infection vary according the age group.

Sign in / Sign up

Export Citation Format

Share Document