scholarly journals Human Metapneumovirus Establishes Persistent Infection in the Lungs of Mice and Is Reactivated by Glucocorticoid Treatment

2009 ◽  
Vol 83 (13) ◽  
pp. 6837-6848 ◽  
Author(s):  
Yuru Liu ◽  
Debra L. Haas ◽  
Spencer Poore ◽  
Sanjin Isakovic ◽  
Michelle Gahan ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Human Metapneumovirus ◽  
Respiratory Epithelial Cells ◽  
Glucocorticoid Treatment ◽  
Hmpv Infection ◽  
Neuronal Processes ◽  
Infected Cells ◽  
Syncytial Virus ◽  
Tract Infections ◽  
Respiratory Epithelial

ABSTRACT Human metapneumovirus (HMPV) has been identified as a worldwide agent of serious upper and lower respiratory tract infections in infants and young children. HMPV is second only to respiratory syncytial virus (RSV) as a leading cause of bronchiolitis, and, like RSV, consists of two major genotypes that cocirculate and vary among communities year to year. Children who have experienced acute HMPV infection may develop sequelae of wheezing and asthma; however, the features contributing to this pathology remain unknown. A possible mechanism for postbronchiolitis disease is that HMPV might persist in the lung providing a stimulus that could contribute to wheezing and asthma. Using immunohistochemistry to identify HMPV-infected cells in the lungs of mice, we show that HMPV mediates biphasic replication in respiratory epithelial cells then infection migrates to neuronal processes that innervate the lungs where the virus persists with no detectable infection in epithelial cells. After glucocorticoid treatment, the virus is reactivated from neural fibers and reinfects epithelial cells. The findings show that HMPV persists in neural fibers and suggest a mechanism for disease chronicity that has important implications for HMPV disease intervention strategies.

scholarly journals Dolosigranulum pigrum Modulates Immunity against SARS-CoV-2 in Respiratory Epithelial Cells

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 634
Author(s):  
Md. Aminul Islam ◽  
Leonardo Albarracin ◽  
Vyacheslav Melnikov ◽  
Bruno G. N. Andrade ◽  
Rafael R. C. Cuadrat ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Specific Effect ◽  
Commensal Bacteria ◽  
Cellular Damage ◽  
Poly I:C ◽  
Respiratory Epithelial Cells ◽  
Promising Alternative ◽  
Immunological Mechanisms ◽  
Syncytial Virus ◽  
Respiratory Epithelial

In a previous work, we demonstrated that nasally administered Dolosigranulum pigrum 040417 beneficially modulated the respiratory innate immune response triggered by the activation of Toll-like receptor 3 (TLR3) and improved protection against Respiratory Syncytial Virus (RSV) in mice. In this work, we aimed to evaluate the immunomodulatory effects of D. pigrum 040417 in human respiratory epithelial cells and the potential ability of this immunobiotic bacterium to increase the protection against Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The respiratory commensal bacterium D. pigrum 040417 differentially modulated the production of IFN-β, IL-6, CXCL8, CCL5 and CXCL10 in the culture supernatants of Calu-3 cells stimulated with poly(I:C) or challenged with SARS-CoV-2. The differential cytokine profile induced by the 040417 strain was associated with a significant reduction in viral replication and cellular damage after coronavirus infection. Of note, D. pigrum 030918 was not able to modify the resistance of Calu-3 cells to SARS-CoV-2 infection, indicating a strain-specific immunomodulatory effect for respiratory commensal bacteria. The findings of this work improve our understanding of the immunological mechanisms involved in the modulation of respiratory immunity induced by respiratory commensal bacteria, by demonstrating their specific effect on respiratory epithelial cells. In addition, the results suggest that particular strains such as D. pigrum 040417 could be used as a promising alternative for combating SARS-CoV-2 and reducing the severity of COVID-19.

scholarly journals Immunobiotic Lactobacilli Improve Resistance of Respiratory Epithelial Cells to SARS-CoV-2 Infection

Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1197
Author(s):  
Md. Aminul Islam ◽  
Leonardo Albarracin ◽  
Mikado Tomokiyo ◽  
Juan Carlos Valdez ◽  
Jacinto Sacur ◽  
...  
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Poly I:C ◽  
Respiratory Pathogens ◽  
Respiratory Epithelial Cells ◽  
Beneficial Effects ◽  
In Vivo Experiments ◽  
Syncytial Virus ◽  
Respiratory Epithelial

Previously, we reported that immunomodulatory lactobacilli, nasally administered, beneficially regulated the lung antiviral innate immune response induced by Toll-like receptor 3 (TLR3) activation and improved protection against the respiratory pathogens, influenza virus and respiratory syncytial virus in mice. Here, we assessed the immunomodulatory effects of viable and non-viable Lactiplantibacillus plantarum strains in human respiratory epithelial cells (Calu-3 cells) and the capacity of these immunobiotic lactobacilli to reduce their susceptibility to the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Immunobiotic L. plantarum MPL16 and CRL1506 differentially modulated IFN-β, IL-6, CXCL8, CCL5 and CXCL10 production and IFNAR2, DDX58, Mx1 and OAS1 expression in Calu-3 cells stimulated with the TLR3 agonist poly(I:C). Furthermore, the MPL16 and CRL1506 strains increased the resistance of Calu-3 cells to the challenge with SARS-CoV-2. L. plantarum MPL16 induced these beneficial effects more efficiently than the CRL1506 strain. Of note, neither non-viable MPL16 and CRL1506 strains nor the non-immunomodulatory strains L. plantarum CRL1905 and MPL18 could modify the resistance of Calu-3 cells to SARS-CoV-2 infection or the immune response to poly(I:C) challenge. To date, the potential beneficial effects of immunomodulatory probiotics on SARS-CoV-2 infection and COVID-19 outcome have been extrapolated from studies carried out in the context of other viral pathogens. To the best of our knowledge, this is the first demonstration of the ability of immunomodulatory lactobacilli to positively influence the replication of the new coronavirus. Further mechanistic studies and in vivo experiments in animal models of SARS-CoV-2 infection are necessary to identify specific strains of beneficial immunobiotic lactobacilli like L. plantarum MPL16 or CRL1506 for the prevention or treatment of the COVID-19.

scholarly journals Human Metapneumovirus Impairs Apoptosis of Nasal Epithelial Cells in Asthma via HSP70

2016 ◽  
Vol 9 (1) ◽  
pp. 52-64 ◽  
Author(s):  
Engin Baturcam ◽  
Natale Snape ◽  
Tiong Han Yeo ◽  
Johanna Schagen ◽  
Emma Thomas ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Viral Infections ◽  
Airway Epithelial Cells ◽  
Human Metapneumovirus ◽  
Airway Epithelial ◽  
Caspase Activation ◽  
Nasal Epithelial Cells ◽  
Hmpv Infection ◽  
Syncytial Virus

Asthmatics are highly susceptible to respiratory viral infections, possibly due to impaired innate immunity. However, the exact mechanisms of susceptibility are likely to differ amongst viruses. Therefore, we infected primary nasal epithelial cells (NECs) from adults with mild-to-moderate asthma, with respiratory syncytial virus (RSV) or human metapneumovirus (hMPV) in vitro and investigated the antiviral response. NECs from these asthmatics supported elevated hMPV but not RSV infection, compared to non-asthmatic controls. This correlated with reduced apoptosis and reduced activation of caspase-9 and caspase-3/7 in response to hMPV, but not RSV. The expression of heat shock protein 70 (HSP70), a known inhibitor of caspase activation and subsequent apoptosis, was amplified in response to hMPV infection. Chemical inhibition of HSP70 function restored caspase activation and reduced hMPV infection in NECs from asthmatic subjects. There was no impairment in the production of IFN by NECs from asthmatics in response to either hMPV or RSV, demonstrating that increased infection of asthmatic airway cells by hMPV is IFN-independent. This study demonstrates, for the first time, a mechanism for elevated hMPV infection in airway epithelial cells from adult asthmatics and identifies HSP70 as a potential target for antiviral and asthma therapies.

Respiratory Epithelial Cells Can Remember Infection: A Proof of Concept Study

2019 ◽  
Author(s):  
Jeanne Bigot ◽  
Loic Guillot ◽  
Juliette Guitard ◽  
Manon Ruffin ◽  
Harriet Corvol ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Respiratory Tract Infections ◽  
Innate Immune ◽  
Immune Memory ◽  
Proof Of Concept ◽  
Respiratory Epithelial Cells ◽  
Bronchial Epithelial ◽  
Previous Contact ◽  
Tract Infections ◽  
Respiratory Epithelial

Abstract Human bronchial epithelial cells play a key role in airway immune homeostasis. We hypothesized that these sentinel cells can remember a previous contact with pathogen compounds and respond nonspecifically to reinfection, a phenomenon called innate immune memory. We demonstrated that their pre-exposure to Pseudomonas aeruginosa flagellin modify their inflammatory response to a second, non-related stimulus, including live pathogens or lipopolysaccharide. Using histone acetyltransferase and methyltransferase inhibitors, we showed that this phenomenon relied on epigenetic regulation. This report is a major breakthrough in the field of multi-microbial respiratory tract infections, wherein control of inflammatory exacerbations is a major therapeutic issue.

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