How the Respiratory Epithelium Senses and Reacts to Influenza Virus

Benam, Kambez H.; Denney, Laura; Ho, Ling‐Pei

doi:10.1165/rcmb.2018-0247tr

Cited by 25 publications

(19 citation statements)

References 165 publications

(191 reference statements)

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“…This type 1 IFN then ligates the IFN receptor (IFNAR) on the same or neighbouring cells and cause transcription of hundreds more ISGs which directly interfere with pathogen replication and also activates other immune pathways. This potent and early immune defence pathway unleashes a large number of cytokines, chemokines ( 31 , 32 ), and also enhances natural killer cell function and high affinity T and B cell responses ( 28 ). In non-infectious settings, when Type 1 IFN signaling is persistently activated [e.g., due to the recognition of self-nucleic acid in systemic lupus erythematosus or abnormal nucleic acid species in Aicardia-Goutieres syndrome (AGS)] severe inflammation and clinicopathologic manifestations can ensue ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

Multi-Modal Characterization of Monocytes in Idiopathic Pulmonary Fibrosis Reveals a Primed Type I Interferon Immune Phenotype

et al. 2021

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Idiopathic pulmonary fibrosis (IPF) is the most severe form of chronic lung fibrosis. Circulating monocytes have been implicated in immune pathology in IPF but their phenotype is unknown. In this work, we determined the immune phenotype of monocytes in IPF using multi-colour flow cytometry, RNA sequencing and corresponding serum factors, and mapped the main findings to amount of lung fibrosis and single cell transcriptomic landscape of myeloid cells in IPF lungs. We show that monocytes from IPF patients displayed increased expression of CD64 (FcγR1) which correlated with amount of lung fibrosis, and an amplified type I IFN response ex vivo. These were accompanied by markedly raised CSF-1 levels, IL-6, and CCL-2 in serum of IPF patients. Interrogation of single cell transcriptomic data from human IPF lungs revealed increased proportion of CD64hi monocytes and “transitional macrophages” with higher expression of CCL-2 and type I IFN genes. Our study shows that monocytes in IPF patients are phenotypically distinct from age-matched controls, with a primed type I IFN pathway that may contribute to driving chronic inflammation and fibrosis. These findings strengthen the potential role of monocytes in the pathogenesis of IPF.

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Section: Discussionmentioning

confidence: 99%

Multi-Modal Characterization of Monocytes in Idiopathic Pulmonary Fibrosis Reveals a Primed Type I Interferon Immune Phenotype

et al. 2021

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“…The type 1 IFN (endogenously produced by the cell via this pathway or from other cells) then ligates the IFN receptor (IFNAR) and results in hundreds of ISGs which directly interfere with pathogen replication and also activates other immune pathways to combat infection (31,32). This highly potent immune defence pathway unleashes a large number of cytokines, chemokines (43)(44)(45), and also enhances natural killer cell function and high affinity T and B cell responses (46). In noninfectious settings, Type 1 IFN signalling can be persistently activated [e.g.…”

Section: Discussionmentioning

confidence: 99%

Type-1 IFN primed monocytes in pathogenesis of idiopathic pulmonary fibrosis

Fraser

Denney

Blirando

et al. 2020

Preprint

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Idiopathic pulmonary fibrosis (IPF) is the most severe form of lung fibrosis. It is progressive, and has an extremely poor outcome and limited treatment options. The disease exclusively affects the lungs, and thus less attention has been focused on blood-borne immune cells.which could be a more effective therapeutic target than lung-based cells. Here, we questioned if circulating monocytes, which has been shown to be increased in IPF, bore abnormalities that might contribute to its pathogenesis. We found that levels of circulating monocytes correlated directly with the extent of fibrosis in the lungs, and increased further during acute clinical deterioration. Monocytes in IPF were phenotypically distinct, displaying increased expression of CD64, a type 1 IFN gene expression signature and a greater magnitude of type 1 IFN response when stimulated. These abnormalities were accompanied by markedly raised CSF-1 levels in the serum, prolonged survival of monocytes ex vivo, and increased numbers of monocytes in lung tissue. Our study defines the key monocytic abnormalities in IPF, proposing type 1 IFN-primed monocytes as a potential driver of an aberrant repair response and fibrosis. It provides a rationale for targeting monocytes and identifies monocytic CD64 as a potential specific therapeutic target for IPF.

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“…Th1 cells, for its part, secrete the cytokines TNF-α and IL-2. Cytotoxic CD8 + T-lymphocytes recognize the viral antigen of the infected cell within the MHC class I molecules, which is present on most cells, leading to (1) the release of the antiviral cytokines TNF-α and INF type I (INF-α), ( 2) release of cytotoxic granules with proteases leading to the apoptosis of the virus-infected cell and (3) activation of the caspase cascade and death of the target cell via Fas/FasL interaction of signaling molecules on the surface of activated CD8 + T-lymphocytes [29,30,100].…”

Section: Respiratory and Immune System Response To Sars-cov-2mentioning

confidence: 99%

Respiratory epithelium: Place of entry and / or defense against SARS-CoV-2 virus

Leštarević¹,

Savić²,

Vitković³

et al. 2020

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Coronavirus Disease (COVID-19) is caused by the RNA virus SARS-CoV-2. The primary receptor for the virus is most likely Angiotensin-converting enzyme 2 (ACE2), and the virus enters the body by infecting epithelial cells of the respiratory tract. Through the activation of Toll Like Receptors (TLRs), epithelial cells begin to synthesize various biologically active molecules. The pathophysiology of the COVID 19 is primarily attributed to the hyperactivation of host's immune system due to direct damage to the cells, with consequent release of proinflammatory substances, but also due to the activation of the innate immune response through the activation of alveolar macrophages and dendrite cells (DC). A strong proinflammatory reaction causes damage to alveolar epithelial cells and vascular endothelium. Respiratory epithelial cells, alveolar macrophages and DC are likely to be the most important cells involved in the innate immune response to the virus, since prolonged and excessive SARS-CoV-2-induced activation of these cells leads to the secretion of cytokines and chemokines that massively attract leukocytes and monocytes to the lungs and cause lung damage.

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How the Respiratory Epithelium Senses and Reacts to Influenza Virus

Cited by 25 publications

References 165 publications

Multi-Modal Characterization of Monocytes in Idiopathic Pulmonary Fibrosis Reveals a Primed Type I Interferon Immune Phenotype

Multi-Modal Characterization of Monocytes in Idiopathic Pulmonary Fibrosis Reveals a Primed Type I Interferon Immune Phenotype

Type-1 IFN primed monocytes in pathogenesis of idiopathic pulmonary fibrosis

Respiratory epithelium: Place of entry and / or defense against SARS-CoV-2 virus

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