scholarly journals Hamster organotypic modeling of SARS-CoV-2 lung and brainstem infection

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marion Ferren ◽  
Valérie Favède ◽  
Didier Decimo ◽  
Mathieu Iampietro ◽  
Nicole A. P. Lieberman ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infection ◽  
Tissue Level ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Organotypic Cultures ◽  
Neurological Sequelae ◽  
Global Pandemic ◽  
Rapid Modeling ◽  
The Brain

AbstractSARS-CoV-2 has caused a global pandemic of COVID-19 since its emergence in December 2019. The infection causes a severe acute respiratory syndrome and may also spread to central nervous system leading to neurological sequelae. We have developed and characterized two new organotypic cultures from hamster brainstem and lung tissues that offer a unique opportunity to study the early steps of viral infection and screening antivirals. These models are not dedicated to investigate how the virus reaches the brain. However, they allow validating the early tropism of the virus in the lungs and demonstrating that SARS-CoV-2 could infect the brainstem and the cerebellum, mainly by targeting granular neurons. Viral infection induces specific interferon and innate immune responses with patterns specific to each organ, along with cell death by apoptosis, necroptosis, and pyroptosis. Overall, our data illustrate the potential of rapid modeling of complex tissue-level interactions during infection by a newly emerged virus.

scholarly journals Organotypic modeling of SARS-CoV-2 lung and brainstem infection

2020 ◽  
Author(s):  
Marion Ferren ◽  
Valérie Favede ◽  
Didier Decimo ◽  
Mathieu Iampietro ◽  
Nicole A. P. Lieberman ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Immune Responses ◽  
Viral Infection ◽  
Central Nervous System Infection ◽  
Tissue Level ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Organotypic Cultures ◽  
Neurological Sequelae ◽  
Global Pandemic

Abstract SARS-CoV-2 has caused a global pandemic of Covid-19 since its emergence in December 2019. The infection causes a severe acute respiratory syndrome and may also lead to central nervous system infection and neurological sequelae. We developed and characterized two new organotypic cultures from hamster brainstem and lung tissues that offer the unique opportunity to study the early steps of the pathogenesis and screening of antivirals. Using these models, we validated the early tropism of the virus in the lung and demonstrated that SARS-CoV2 can infect brainstem and cerebellum, mainly by targeting granular neurons. Viral infection induced specific interferon and innate immune responses with patterns specific to each organ along with apoptotic, necroptotic, and pyroptotic cell death. Overall, our data illustrate the potential of rapidly modeling complex tissue level interactions of viral infection in a newly emerged virus.

scholarly journals Evidence for Differential Roles for NKG2D Receptor Signaling in Innate Host Defense against Coronavirus-Induced Neurological and Liver Disease

2007 ◽  
Vol 82 (6) ◽  
pp. 3021-3030 ◽  
Author(s):  
Kevin B. Walsh ◽  
Melissa B. Lodoen ◽  
Robert A. Edwards ◽  
Lewis L. Lanier ◽  
Thomas E. Lane
Keyword(s):  
Liver Disease ◽  
Immune Responses ◽  
Host Defense ◽  
Nk Cell ◽  
Hepatitis Virus ◽  
Innate Immune ◽  
Liver Pathology ◽  
Innate Immune Responses ◽  
Ifn Γ ◽  
The Brain

ABSTRACT Infection of SCID mice with a recombinant murine coronavirus (mouse hepatitis virus [MHV]) expressing the T-cell chemoattractant CXC chemokine ligand 10 (CXCL10) resulted in increased survival and reduced viral burden within the brain and liver compared to those of mice infected with an isogenic control virus (MHV), supporting an important role for CXCL10 in innate immune responses following viral infection. Enhanced protection in MHV-CXCL10-infected mice correlated with increased gamma interferon (IFN-γ) production by infiltrating natural killer (NK) cells within the brain and reduced liver pathology. To explore the underlying mechanisms associated with protection from disease in MHV-CXCL10-infected mice, the functional contributions of the NK cell-activating receptor NKG2D in host defense were examined. The administration of an NKG2D-blocking antibody to MHV-CXCL10-infected mice did not reduce survival, dampen IFN-γ production in the brain, or affect liver pathology. However, NKG2D neutralization increased viral titers within the liver, suggesting a protective role for NKG2D signaling in this organ. These data indicate that (i) CXCL10 enhances innate immune responses, resulting in protection from MHV-induced neurological and liver disease; (ii) elevated NK cell IFN-γ expression in the brain of MHV-CXCL10-infected mice occurs independently of NKG2D; and (iii) NKG2D signaling promotes antiviral activity within the livers of MHV-infected mice that is not dependent on IFN-γ and tumor necrosis factor alpha secretion.

scholarly journals “Corneal Nerves, CD11c+ Dendritic Cells and Their Impact on Ocular Immune Privilege”

2021 ◽  
Vol 12 ◽  
Author(s):  
Jerry Y. Niederkorn
Keyword(s):  
Immune Responses ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Immune Privilege ◽  
Innate Immune Responses ◽  
Regulatory Processes ◽  
Immune Mediated ◽  
Corneal Nerves ◽  
The Central Nervous System ◽  
The Brain

The eye and the brain have limited capacities for regeneration and as such, immune-mediated inflammation can produce devastating consequences in the form of neurodegenerative diseases of the central nervous system or blindness as a result of ocular inflammatory diseases such as uveitis. Accordingly, both the eye and the brain are designed to limit immune responses and inflammation – a condition known as “immune privilege”. Immune privilege is sustained by physiological, anatomical, and regulatory processes that conspire to restrict both adaptive and innate immune responses.

scholarly journals Host–Viral Interactions in the Pathogenesis of Ulcerative Colitis

2021 ◽  
Vol 22 (19) ◽  
pp. 10851
Author(s):  
Torunn Bruland ◽  
Ann Elisabet Østvik ◽  
Arne Kristian Sandvik ◽  
Marianne Doré Hansen
Keyword(s):  
Ulcerative Colitis ◽  
Immune Responses ◽  
Viral Infection ◽  
Protective Immunity ◽  
Innate Immune ◽  
The Other ◽  
Mucosal Inflammation ◽  
Innate Immune Responses ◽  
Rapid Release ◽  
Viral Interactions

Ulcerative colitis is characterized by relapsing and remitting colonic mucosal inflammation. During the early stages of viral infection, innate immune defenses are activated, leading to the rapid release of cytokines and the subsequent initiation of downstream responses including inflammation. Previously, intestinal viruses were thought to be either detrimental or neutral to the host. However, persisting viruses may have a role as resident commensals and confer protective immunity during inflammation. On the other hand, the dysregulation of gut mucosal immune responses to viruses can trigger excessive, pathogenic inflammation. The purpose of this review is to discuss virus-induced innate immune responses that are at play in ulcerative colitis.

scholarly journals Circadian regulation of the Drosophila astrocyte transcriptome

PLoS Genetics ◽  
2021 ◽  
Vol 17 (9) ◽  
pp. e1009790
Author(s):  
Samantha You ◽  
Alder M. Yu ◽  
Mary A. Roberts ◽  
Ivanna J. Joseph ◽  
F. Rob Jackson
Keyword(s):  
Immune Responses ◽  
Transcriptional Profiling ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Sleep Behavior ◽  
Circadian Control ◽  
Number Of Genes ◽  
Cell Type Specific ◽  
Normal Sleep ◽  
The Brain

Recent studies have demonstrated that astrocytes cooperate with neurons of the brain to mediate circadian control of many rhythmic processes including locomotor activity and sleep. Transcriptional profiling studies have described the overall rhythmic landscape of the brain, but few have employed approaches that reveal heterogeneous, cell-type specific rhythms of the brain. Using cell-specific isolation of ribosome-bound RNAs in Drosophila, we constructed the first circadian “translatome” for astrocytes. This analysis identified 293 “cycling genes” in astrocytes, most with mammalian orthologs. A subsequent behavioral genetic screen identified a number of genes whose expression is required in astrocytes for normal sleep behavior. In particular, we show that certain genes known to regulate fly innate immune responses are also required for normal sleep patterns.

scholarly journals Innate Immune Responses against Viral Infection and Its Suppression by Viral Proteins

2013 ◽  
Vol 133 (3) ◽  
pp. 323-328
Author(s):  
Hiroyuki Oshiumi ◽  
Misako Matsumoto ◽  
Tsukasa Seya
Keyword(s):  
Immune Responses ◽  
Viral Infection ◽  
Viral Proteins ◽  
Innate Immune ◽  
Innate Immune Responses

scholarly journals Hantaviruses Induce Antiviral and Pro-Inflammatory Innate Immune Responses in Astrocytic Cells and the Brain

2014 ◽  
Vol 27 (6) ◽  
pp. 256-266 ◽  
Author(s):  
Ok Sarah Shin ◽  
Gabriella Shinyoung Song ◽  
Mukesh Kumar ◽  
Richard Yanagihara ◽  
Ho-Wang Lee ◽  
...  
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
The Brain

scholarly journals Cocaine-induced release of CXCL10 from pericytes regulates monocyte transmigration into the CNS

2019 ◽  
Vol 218 (2) ◽  
pp. 700-721 ◽  
Author(s):  
Fang Niu ◽  
Ke Liao ◽  
Guoku Hu ◽  
Susmita Sil ◽  
Shannon Callen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Active Components ◽  
Barrier Integrity ◽  
Enhanced Secretion ◽  
First Time ◽  
The Brain

Cocaine is known to facilitate the transmigration of inflammatory leukocytes into the brain, an important mechanism underlying neuroinflammation. Pericytes are well-recognized as important constituents of the blood–brain barrier (BBB), playing a key role in maintaining barrier integrity. In the present study, we demonstrate for the first time that exposure of human brain vascular pericytes to cocaine results in enhanced secretion of CXCL10, leading, in turn, to increased monocyte transmigration across the BBB both in vitro and in vivo. This process involved translocation of σ-1 receptor (σ-1R) and interaction of σ-1R with c-Src kinase, leading to activation of the Src–PDGFR-β–NF-κB pathway. These findings imply a novel role for pericytes as a source of CXCL10 in the pericyte–monocyte cross talk in cocaine-mediated neuroinflammation, underpinning their role as active components of the innate immune responses.

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