scholarly journals SARS-CoV-2 infection in the Syrian hamster model causes inflammation as well as type I interferon dysregulation in both respiratory and non-respiratory tissues including the heart and kidney

2021 ◽  
Vol 17 (7) ◽  
pp. e1009705
Author(s):  
Magen Ellen Francis ◽  
Una Goncin ◽  
Andrea Kroeker ◽  
Cynthia Swan ◽  
Robyn Ralph ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Clinical Symptoms ◽  
Type I Interferons ◽  
Host Responses ◽  
Type I ◽  
Hamster Model ◽  
Organ Systems ◽  
Major Organ ◽  
Kidney Liver ◽  
Multiorgan Disease

COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is a disease affecting several organ systems. A model that captures all clinical symptoms of COVID-19 as well as long-haulers disease is needed. We investigated the host responses associated with infection in several major organ systems including the respiratory tract, the heart, and the kidneys after SARS-CoV-2 infection in Syrian hamsters. We found significant increases in inflammatory cytokines (IL-6, IL-1beta, and TNF) and type II interferons whereas type I interferons were inhibited. Examination of extrapulmonary tissue indicated inflammation in the kidney, liver, and heart which also lacked type I interferon upregulation. Histologically, the heart had evidence of myocarditis and microthrombi while the kidney had tubular inflammation. These results give insight into the multiorgan disease experienced by people with COVID-19 and possibly the prolonged disease in people with post-acute sequelae of SARS-CoV-2 (PASC).

scholarly journals SARS-CoV-2 infection in the Syrian hamster model causes inflammation as well as type I interferon dysregulation in both respiratory and non-respiratory tissues including the heart and kidney

2021 ◽  
Author(s):  
Magen E. Francis ◽  
Una Goncin ◽  
Andrea Kroeker ◽  
Cynthia Swan ◽  
Robyn Ralph ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Clinical Symptoms ◽  
Type I Interferons ◽  
Host Responses ◽  
Type I ◽  
Hamster Model ◽  
Organ Systems ◽  
Major Organ ◽  
Kidney Liver ◽  
Multiorgan Disease

AbstractCOVID-19 (coronavirus disease 2019) caused SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is a disease affecting several organ systems. A model that captures all clinical symptoms of COVID-19 as well as long-haulers disease is needed. We investigated the host responses associated with infection in several major organ systems including the respiratory tract, the heart, and the kidneys after SARS-CoV-2 infection in Syrian hamsters. We found significant increases in inflammatory cytokines (IL-6, IL-1beta, and TNF) and type II interferons whereas type I interferons were inhibited. Examination of extrapulmonary tissue indicated inflammation in the kidney, liver, and heart which also lacked type I interferon upregulation. Histologically, the heart had evidence of mycarditis and microthrombi while the kidney had tubular inflammation. These results give insight into the multiorgan disease experienced by people with COVID-19 and possibly the prolonged disease in people with post-acute sequelae of SARS-CoV-2 (PASC).

scholarly journals Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model

2021 ◽  
Author(s):  
Pierre Bessière ◽  
Marine Wasniewski ◽  
Evelyne Picard-Meyer ◽  
Alexandre Servat ◽  
Thomas Figueroa ◽  
...  
Keyword(s):  
Post Infection ◽  
Intranasal Administration ◽  
Type I Interferon ◽  
Clinical Signs ◽  
Type I Interferons ◽  
Type I ◽  
Interferon Treatment ◽  
Hamster Model ◽  
Critical Determinant ◽  
Recombinant Type

AbstractImpaired type I interferons (IFNs) production or signaling have been associated with severe COVID-19, further promoting the evaluation of recombinant type I IFNs as therapeutics against SARS-CoV-2 infection. In the Syrian hamster model, we show that intranasal administration of IFN-α starting one day pre-infection or one day post-infection limited weight loss and decreased viral lung titers. By contrast, intranasal administration of IFN-α starting at the onset of symptoms three days post-infection had no impact on the clinical course of SARS-CoV-2 infection. Our results provide evidence that early type I IFN treatments are beneficial, while late interventions are ineffective, although not associated with signs of enhanced disease.One Sentence SummaryThe timing of type I interferon treatment is a critical determinant of its efficacy against SARS-CoV-2 infection.

scholarly journals Complexities of Type I Interferon Biology: Lessons from LCMV

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 172 ◽  
Author(s):  
Tamara Suprunenko ◽  
Markus Hofer
Keyword(s):  
Molecular Mechanisms ◽  
Viral Infections ◽  
Type I Interferon ◽  
Malignant Tumors ◽  
Antiviral Immunity ◽  
Lymphocytic Choriomeningitis ◽  
Type I Interferons ◽  
Host Responses ◽  
Type I ◽  
Novel Treatments

Over the past decades, infection of mice with lymphocytic choriomeningitis virus (LCMV) has provided an invaluable insight into our understanding of immune responses to viruses. In particular, this model has clarified the central roles that type I interferons play in initiating and regulating host responses. The use of different strains of LCMV and routes of infection has allowed us to understand how type I interferons are critical in controlling virus replication and fostering effective antiviral immunity, but also how they promote virus persistence and functional exhaustion of the immune response. Accordingly, these discoveries have formed the foundation for the development of novel treatments for acute and chronic viral infections and even extend into the management of malignant tumors. Here we review the fundamental insights into type I interferon biology gained using LCMV as a model and how the diversity of LCMV strains, dose, and route of administration have been used to dissect the molecular mechanisms underpinning acute versus persistent infection. We also identify gaps in the knowledge regarding LCMV regulation of antiviral immunity. Due to its unique properties, LCMV will continue to remain a vital part of the immunologists’ toolbox.

Type I interferons directly regulate lymphocyte recirculation and cause transient blood lymphopenia

Blood ◽  
2006 ◽  
Vol 108 (10) ◽  
pp. 3253-3261 ◽  
Author(s):  
Elisabeth Kamphuis ◽  
Tobias Junt ◽  
Zoe Waibler ◽  
Reinhold Forster ◽  
Ulrich Kalinke
Keyword(s):  
T Cell ◽  
Type I Interferon ◽  
Clinical Symptoms ◽  
Type I Interferons ◽  
Poly I:C ◽  
Adhesion Assay ◽  
Type I ◽  
Tlr Agonists ◽  
Tnf Α ◽  
T Cell Lymphopenia

Abstract Early viral infection is often associated with lymphopenia, a transient reduction of blood lymphocyte counts long before the onset of clinical symptoms. We have investigated lymphopenia in mice infected with vesicular stomatitis virus (VSV) or treated with the Toll-like receptor (TLR) agonists poly(I:C) and R-848. In all cases analyzed, lymphopenia was critically dependent on type I interferon receptor (IFNAR) signaling. With the use of bone marrow–chimeric mice, radioresistant cells, such as stroma and endothelium, could be excluded as type I interferon (IFN-α/β) targets for the induction of lymphopenia. Instead, adoptive transfer experiments and studies in conditionally gene-targeted mice with a B- or T-cell–specific IFNAR deletion demonstrated that IFN-α/β exerted a direct effect on lymphocytes that was necessary and largely sufficient to induce lymphopenia. Furthermore, after treatment with R-848, we found that other cytokines such as TNF-α also played a role in T-cell lymphopenia. Investigation of the molecular mechanism revealed that lymphopenia was mainly independent of G protein–coupled receptors (GPCRs) and chemokines. In an adhesion assay, B cells of poly(I:C)–treated mice showed moderately increased adhesion to ICAM-1 but not to VCAM-1. In conclusion, our data identify a new effect of direct IFN-α/β stimulation of lymphocytes that profoundly affects lymphocyte redistribution.

The Role of Toll-Like Receptors and Type I Interferons in Host Responses to Bacteria

2009 ◽  
Vol 5 (2) ◽  
pp. 143-149
Author(s):  
Marja Ojaniemi ◽  
Mari Liljeroos ◽  
Reetta Vuolteenaho
Keyword(s):  
Type I Interferons ◽  
Host Responses ◽  
Type I ◽  
Toll Like Receptors

scholarly journals Characterization of Host Responses against a Recombinant Fowlpox Virus-Vectored Vaccine Expressing the Hemagglutinin Antigen of an Avian Influenza Virus

2010 ◽  
Vol 17 (3) ◽  
pp. 454-463 ◽  
Author(s):  
Hamid R. Hghihghi ◽  
Leah R. Read ◽  
Hakimeh Mohammadi ◽  
Yanlong Pei ◽  
Claudia Ursprung ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Immune Responses ◽  
Avian Influenza Virus ◽  
Cultured Cells ◽  
Type I Interferons ◽  
Host Responses ◽  
Type I ◽  
Fowlpox Virus ◽  
Time Points

ABSTRACT There currently are commercial fowlpox virus (FPV)-vectored vaccines for use in chickens, including TROVAC-AIV H5, which expresses the hemagglutinin (HA) antigen of an avian influenza virus and can confer immunity against avian influenza in chickens. Despite the use of recombinant FPV (rFPV) for vaccine delivery, very little is known about the immune responses generated by these viruses in chickens. The present study was designed to investigate host responses to rFPV in vivo and in vitro. In cultured cells infected with TROVAC-AIV H5, there was an early increase in the expression of type I interferons (IFN), Toll-like receptors 3 and 7 (TLR3 and TLR7, respectively), TRIF, and MyD88, which was followed by a decrease in the expression of these genes at later time points. There also was an increase in the expression of interleukin-1β (IL-1β), IL-8, and beta-defensin genes at early time points postinfection. In chickens immunized with TROVAC-AIV H5, there was higher expression of IFN-γ and IL-10 at day 5 postvaccination in spleen of vaccinated birds than in that of control birds. We further investigated the ability of the vaccine to induce immune responses against the HA antigen and discovered that there was a cell-mediated response elicited in vaccinated chickens against this antigen. The findings of this study demonstrate that FPV-vectored vaccines can elicit a repertoire of responses marked by the early expression of TLRs, type I interferons, and proinflammatory cytokines, as well as cytokines associated with adaptive immune responses. This study provides a platform for designing future generations of rFPV-vectored vaccines.

Type I Interferons in Autoimmune Disease

2019 ◽  
Vol 14 (1) ◽  
pp. 369-393 ◽  
Author(s):  
Mary K. Crow ◽  
Mikhail Olferiev ◽  
Kyriakos A. Kirou
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune System ◽  
Lupus Erythematosus ◽  
Type I Interferon ◽  
Type I Interferons ◽  
Type I ◽  
Systemic Lupus ◽  
Pathway Activation ◽  
Interferon Pathway ◽  
Chronic Activation

Type I interferons, which make up the first cytokine family to be described and are the essential mediators of antivirus host defense, have emerged as central elements in the immunopathology of systemic autoimmune diseases, with systemic lupus erythematosus as the prototype. Lessons from investigation of interferon regulation following virus infection can be applied to lupus, with the conclusion that sustained production of type I interferon shifts nearly all components of the immune system toward pathologic functions that result in tissue damage and disease. We review recent data, mainly from studies of patients with systemic lupus erythematosus, that provide new insights into the mechanisms of induction and the immunologic consequences of chronic activation of the type I interferon pathway. Current concepts implicate endogenous nucleic acids, driving both cytosolic sensors and endosomal Toll-like receptors, in interferon pathway activation and suggest targets for development of novel therapeutics that may restore the immune system to health.

scholarly journals Type I interferon signaling is required for activation of the inflammasome during Francisella infection

2007 ◽  
Vol 204 (5) ◽  
pp. 987-994 ◽  
Author(s):  
Thomas Henry ◽  
Anna Brotcke ◽  
David S. Weiss ◽  
Lucinda J. Thompson ◽  
Denise M. Monack
Keyword(s):  
Cell Death ◽  
Type I Interferon ◽  
Infection Type ◽  
Host Responses ◽  
Inflammasome Activation ◽  
Type I ◽  
Type I Ifn ◽  
Caspase 1 ◽  
Dependent Cell

Francisella tularensis is a pathogenic bacterium whose virulence is linked to its ability to replicate within the host cell cytosol. Entry into the macrophage cytosol activates a host-protective multimolecular complex called the inflammasome to release the proinflammatory cytokines interleukin (IL)-1β and -18 and trigger caspase-1–dependent cell death. In this study, we show that cytosolic F. tularensis subspecies novicida (F. novicida) induces a type I interferon (IFN) response that is essential for caspase-1 activation, inflammasome-mediated cell death, and release of IL-1β and -18. Extensive type I IFN–dependent cell death resulting in macrophage depletion occurs in vivo during F. novicida infection. Type I IFN is also necessary for inflammasome activation in response to cytosolic Listeria monocytogenes but not vacuole-localized Salmonella enterica serovar Typhimurium or extracellular adenosine triphosphate. These results show the specific connection between type I IFN signaling and inflammasome activation, which are two sequential events triggered by the recognition of cytosolic bacteria. To our knowledge, this is the first example of the positive regulation of inflammasome activation. This connection underscores the importance of the cytosolic recognition of pathogens and highlights how multiple innate immunity pathways interact before commitment to critical host responses.

scholarly journals Commensal bacteria promote type I interferon signaling to maintain immune tolerance

2021 ◽  
Author(s):  
Adriana Vasquez Ayala ◽  
Kazuhiko Matsuo ◽  
Chia-Yun Hsu ◽  
Marvic Carrillo Terrazas ◽  
Hiutung Chu
Keyword(s):  
Immune Tolerance ◽  
Type I Interferon ◽  
Host Cells ◽  
Type I Interferons ◽  
Type I ◽  
Type I Ifn ◽  
Interferon Signaling ◽  
Mesenteric Lymph Nodes ◽  
Viral Pathogens ◽  
Physiological Processes

Type I interferons (IFN) play essential roles in numerous physiological processes, acting as central coordinators in the host response against pathogens. Upon sensing of microbial ligands, host cells rapidly activate the type I IFN response to prime innate and adaptive immune responses. Recent studies suggest tonic IFN are maintained by commensal microbes and critical in mounting an effective immune response to viral pathogens. Further, emerging developments have extended an immunoregulatory role of type I IFN in the maintenance of immune homeostasis. Yet whether immunomodulatory bacteria from the gut microbiota operate through IFN signaling to promote immune tolerance remains largely unanswered. Here we show that commensal microbes are necessary to maintain type I IFN responses in intestinal tissues. Specifically, Bacteroides fragilis induced type I IFN response in dendritic cells (DCs) and this pathway is necessary for the induction of IL-10-producing Foxp3+ regulatory T cells (Tregs). In addition, we show upregulation of type I IFN related genes in Tregs from mesenteric lymph nodes and colonic lamina propria of mice colonized with B. fragilis. Our findings demonstrate type I interferon signaling plays an important role in microbiota-mediated immune tolerance in the gut.

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