scholarly journals RNA Sensing of Mycobacterium tuberculosis and Its Impact on TB Vaccination Strategies

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 67 ◽  
Author(s):  
Sanne Burkert ◽  
Ralf R. Schumann
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Type I Interferons ◽  
Immune Memory ◽  
Type I ◽  
Effective Prevention ◽  
Vaccination Strategies ◽  
Host Interaction ◽  
Global Threat ◽  
Antigen Presenting ◽  
The Impact

Tuberculosis (TB) is still an important global threat and although the causing organism has been discovered long ago, effective prevention strategies are lacking. Mycobacterium tuberculosis (MTB) is a unique pathogen with a complex host interaction. Understanding the immune responses upon infection with MTB is crucial for the development of new vaccination strategies and therapeutic targets for TB. Recently, it has been proposed that sensing bacterial nucleic acid in antigen-presenting cells via intracellular pattern recognition receptors (PRRs) is a central mechanism for initiating an effective host immune response. Here, we summarize key findings of the impact of mycobacterial RNA sensing for innate and adaptive host immunity after MTB infection, with emphasis on endosomal toll-like receptors (TLRs) and cytosolic sensors such as NLRP3 and RLRs, modulating T-cell differentiation through IL-12, IL-21, and type I interferons. Ultimately, these immunological pathways may impact immune memory and TB vaccine efficacy. The novel findings described here may change our current understanding of the host response to MTB and potentially impact clinical research, as well as future vaccination design. In this review, the current state of the art is summarized, and an outlook is given on how progress can be made.

scholarly journals Multi-Immune Agonist Nanoparticle Therapy Stimulates Type I Interferons to Activate Antigen-Presenting Cells and Induce Antigen-Specific Antitumor Immunity

2021 ◽  
Vol 18 (3) ◽  
pp. 1014-1025
Author(s):  
Elizabeth S. Levy ◽  
Ryan Chang ◽  
Colin R. Zamecnik ◽  
Miqdad O. Dhariwala ◽  
Lawrence Fong ◽  
...  
Keyword(s):  
Antitumor Immunity ◽  
Antigen Presenting Cells ◽  
Type I Interferons ◽  
Type I ◽  
Antigen Presenting

scholarly journals Route of Infection Determines the Impact of Type I Interferons on Innate Immunity to Listeria monocytogenes

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e65007 ◽  
Author(s):  
Elisabeth Kernbauer ◽  
Verena Maier ◽  
Isabella Rauch ◽  
Mathias Müller ◽  
Thomas Decker
Keyword(s):  
Innate Immunity ◽  
Listeria Monocytogenes ◽  
Type I Interferons ◽  
Type I ◽  
Route Of Infection ◽  
The Impact

scholarly journals Type I Interferons Increase Host Susceptibility to Trypanosoma cruzi Infection

2011 ◽  
Vol 79 (5) ◽  
pp. 2112-2119 ◽  
Author(s):  
Anne-Danielle C. Chessler ◽  
Kacey L. Caradonna ◽  
Akram Da'dara ◽  
Barbara A. Burleigh
Keyword(s):  
Trypanosoma Cruzi ◽  
Parasite Burden ◽  
Host Susceptibility ◽  
Type I Interferons ◽  
Type I ◽  
Type I Ifn ◽  
Content Type ◽  
Type I Ifns ◽  
Ifn Γ ◽  
The Impact

ABSTRACTTrypanosoma cruzi, the protozoan parasite that causes human Chagas' disease, induces a type I interferon (IFN) (IFN-α/β) response during acute experimental infection in mice and in isolated primary cell types. To examine the potential impact of the type I IFN response in shaping outcomes in experimentalT. cruziinfection, groups of wild-type (WT) and type I IFN receptor-deficient (IFNAR−/−) 129sv/ev mice were infected with two differentT. cruzistrains under lethal and sublethal conditions and several parameters were measured during the acute stage of infection. The results demonstrate that type I IFNs are not required for early host protection againstT. cruzi. In contrast, under conditions of lethalT. cruzichallenge, WT mice succumbed to infection whereas IFNAR−/−mice were ultimately able to control parasite growth and survive.T. cruziclearance in and survival of IFNAR−/−mice were accompanied by higher levels of IFN-γ production by isolated splenocytes in response to parasite antigen. The suppression of IFN-γ in splenocytes from WT mice was independent of IL-10 levels. While the impact of type I IFNs on the production of IFN-γ and other cytokines/chemokines remains to be fully determined in the context ofT. cruziinfection, our data suggest that, under conditions of high parasite burden, type I IFNs negatively impact IFN-γ production, initiating a detrimental cycle that contributes to the ultimate failure to control infection. These findings are consistent with a growing theme in the microbial pathogenesis field in which type I IFNs can be detrimental to the host in a variety of nonviral pathogen infection models.

scholarly journals The Cytosolic Sensor cGAS Detects Mycobacterium tuberculosis DNA to Induce Type I Interferons and Activate Autophagy

2015 ◽  
Vol 17 (6) ◽  
pp. 811-819 ◽  
Author(s):  
Robert O. Watson ◽  
Samantha L. Bell ◽  
Donna A. MacDuff ◽  
Jacqueline M. Kimmey ◽  
Elie J. Diner ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Type I Interferons ◽  
Type I

scholarly journals Activation of STING signaling pathway effectively blocks human coronavirus infection

2021 ◽  
Author(s):  
Wei Liu ◽  
Hanako M. Reyes ◽  
June F. Yang ◽  
Yize Li ◽  
Kathleen M. Stewart ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Broad Spectrum ◽  
Type I Interferons ◽  
Type I ◽  
Immune Effector ◽  
Innate Immune Effector ◽  
Coronavirus Infection ◽  
Novel Target ◽  
Sting Pathway ◽  
The Impact

The COVID-19 pandemic poses a serious global health threat. The rapid global spread of SARS-CoV-2 highlights an urgent need to develop effective therapeutics for blocking SARS-CoV-2 infection and spread. Stimulator of Interferon Genes (STING) is a chief element in host antiviral defense pathways. In this study, we examined the impact of the STING signaling pathway on coronavirus infection using the HCoV-OC43 model. We found that HCoV-OC43 infection did not stimulate the STING signaling pathway, but the activation of STING signaling effectively inhibits HCoV-OC43 infection to a much greater extent than that of type I interferons (IFNs). We also discovered that IRF3, the key STING downstream innate immune effector, is essential for this anti-coronavirus activity. In addition, we found that the amidobenzimidazole (ABZI)-based human STING agonist (diABZI) robustly blocks the infection of not only HCoV-OC43 but also SARS-CoV-2. Therefore, our study identifies the STING signaling pathway as a potential therapeutic target that could be exploited for developing broad-spectrum antiviral therapeutics against multiple coronavirus strains in order to face the challenge of future coronavirus outbreaks. Importance The highly infectious and lethal SARS-CoV-2 is posing an unprecedented threat to public health. Other coronaviruses are likely to jump from a non-human animal to humans in the future. Novel broad-spectrum antiviral therapeutics are therefore needed to control known pathogenic coronaviruses such as SARS-CoV-2 and its newly mutated variants, as well as future coronavirus outbreaks. STING signaling is a well-established host defense pathway, but its role in coronavirus infection remains unclear. In the present study, we found that activation of the STING signaling pathway robustly inhibits infection of HCoV-OC43 and SARS-CoV-2. These results identified the STING pathway as a novel target for controlling the spread of known pathogenic coronaviruses as well as emerging coronavirus outbreaks.

scholarly journals Impact of STING Inflammatory Signaling during Intracellular Bacterial Infections

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 74
Author(s):  
Erika S. Guimarães ◽  
Fabio V. Marinho ◽  
Nina M. G. P. de Queiroz ◽  
Maísa M. Antunes ◽  
Sergio C. Oliveira
Keyword(s):  
Immune Responses ◽  
Bacterial Infections ◽  
Inflammatory Responses ◽  
Metabolic Reprogramming ◽  
Host Cells ◽  
Type I Interferons ◽  
Type I ◽  
Bacterial Survival ◽  
Inflammatory Profile ◽  
The Impact

The early detection of bacterial pathogens through immune sensors is an essential step in innate immunity. STING (Stimulator of Interferon Genes) has emerged as a key mediator of inflammation in the setting of infection by connecting pathogen cytosolic recognition with immune responses. STING detects bacteria by directly recognizing cyclic dinucleotides or indirectly by bacterial genomic DNA sensing through the cyclic GMP-AMP synthase (cGAS). Upon activation, STING triggers a plethora of powerful signaling pathways, including the production of type I interferons and proinflammatory cytokines. STING activation has also been associated with the induction of endoplasmic reticulum (ER) stress and the associated inflammatory responses. Recent reports indicate that STING-dependent pathways participate in the metabolic reprogramming of macrophages and contribute to the establishment and maintenance of a robust inflammatory profile. The induction of this inflammatory state is typically antimicrobial and related to pathogen clearance. However, depending on the infection, STING-mediated immune responses can be detrimental to the host, facilitating bacterial survival, indicating an intricate balance between immune signaling and inflammation during bacterial infections. In this paper, we review recent insights regarding the role of STING in inducing an inflammatory profile upon intracellular bacterial entry in host cells and discuss the impact of STING signaling on the outcome of infection. Unraveling the STING-mediated inflammatory responses can enable a better understanding of the pathogenesis of certain bacterial diseases and reveal the potential of new antimicrobial therapy.

scholarly journals Role of Type I Interferons on Filovirus Pathogenesis

Vaccines ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 22 ◽  
Author(s):  
Beatriz Escudero-Pérez ◽  
César Muñoz-Fontela
Keyword(s):  
Animal Models ◽  
Immune Responses ◽  
Marburg Virus ◽  
Type I Interferons ◽  
Type I ◽  
Adaptive Immune ◽  
Antigen Presenting

Filoviruses, such as Ebola and Marburg virus, encode viral proteins with the ability to counteract the type I interferon (IFN-I) response. These IFN-I antagonist proteins are crucial to ensure virus replication, prevent an antiviral state in infected and bystander cells, and impair the ability of antigen-presenting cells to initiate adaptive immune responses. However, in recent years, a number of studies have underscored the conflicting data between in vitro studies and in vivo data obtained in animal models and clinical studies during outbreaks. This review aims to summarize these data and to discuss the relative contributions of IFN-α and IFN-β to filovirus pathogenesis in animal models and humans. Finally, we evaluate the putative utilization of IFN-I in post-exposure therapy and its implications as a biomarker of vaccine efficacy.

scholarly journals Preventing the Risk of Hospitalization for Respiratory Complications of Influenza among the Elderly: Is There a Better Influenza Vaccination Strategy? A Retrospective Population Study

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 344
Author(s):  
Silvia Cocchio ◽  
Tolinda Gallo ◽  
Stefania Del Zotto ◽  
Elena Clagnan ◽  
Andrea Iob ◽  
...  
Keyword(s):  
Influenza Vaccination ◽  
Vaccination Strategy ◽  
The Elderly ◽  
Protective Role ◽  
The Body ◽  
Health Concern ◽  
Respiratory Complications ◽  
Effective Prevention ◽  
Vaccination Strategies ◽  
The Impact

Influenza and its complications are an important public health concern, and vaccination remains the most effective prevention measure. However, the efficacy of vaccination depends on several variables, including the type of strategy adopted. The goal of this study was to assess the impact of different influenza vaccination strategies in preventing hospitalizations for influenza and its related respiratory complications. A retrospective cohort study was conducted on data routinely collected by the health services for six consecutive influenza seasons, considering the population aged 65 years or more at the time of their vaccination and living in northeastern Italy. Our analysis concerns 987,266 individuals vaccinated against influenza during the study period. The sample was a mean 78.0 ± 7.7 years old, and 5681 individuals (0.58%) were hospitalized for potentially influenza-related reasons. The hospitalization rate tended to increase over the years, not-significantly peaking in the 2016–2017 flu season (0.8%). Our main findings revealed that hospitalizations related to seasonal respiratory diseases were reduced as the use of the enhanced vaccine increased (R2 = 0.5234; p < 0.001). Multivariate analysis confirmed the significantly greater protective role of the enhanced vaccine over the conventional vaccination strategy, with adjusted Odds Ratio (adj OR) = 0.62 (95% CI: 0.59–0.66). A prior flu vaccination also had a protective role (adj OR: 0.752 (95% CI: 0.70–0.81)). Age, male sex, and H3N2 mismatch were directly associated with a higher risk of hospitalization for pneumonia. In the second part of our analysis, comparing MF59-adjuvanted trivalent inactivated vaccine (MF59-TIV) with conventional vaccines, we considered 479,397 individuals, of which 3176 (0.66%) were admitted to a hospital. The results show that using the former vaccine reduced the risk of hospitalization by 33% (adj OR: 0.67 (95% CI: 0.59–0.75)). This study contributes to the body of evidence of a greater efficacy of enhanced vaccines, and MF59-adjuvanted TIV in particular, over conventional vaccination strategies in the elderly.

scholarly journals Type I Interferons as Regulators of Human Antigen Presenting Cell Functions

Toxins ◽  
2014 ◽  
Vol 6 (6) ◽  
pp. 1696-1723 ◽  
Author(s):  
Sandra Gessani ◽  
Lucia Conti ◽  
Manuela Del Cornò ◽  
Filippo Belardelli
Keyword(s):  
Type I Interferons ◽  
Type I ◽  
Antigen Presenting Cell ◽  
Cell Functions ◽  
Antigen Presenting

scholarly journals Partial Inhibition of Human Immunodeficiency Virus Replication by Type I Interferons: Impact of Cell-to-Cell Viral Transfer

2009 ◽  
Vol 83 (20) ◽  
pp. 10527-10537 ◽  
Author(s):  
Daniela Vendrame ◽  
Marion Sourisseau ◽  
Virginie Perrin ◽  
Olivier Schwartz ◽  
Fabrizio Mammano
Keyword(s):  
Human Immunodeficiency Virus ◽  
Virus Replication ◽  
Type I Interferons ◽  
Human Immunodeficiency Virus Replication ◽  
Type I ◽  
Restriction Factors ◽  
Hiv Replication ◽  
Potent Effect ◽  
Immunodeficiency Virus ◽  
The Impact

ABSTRACT Type I interferons (IFN) inhibit several steps of the human immunodeficiency virus type 1 (HIV) replication cycle. Some HIV proteins, like Vif and Vpu, directly counteract IFN-induced restriction factors. Other mechanisms are expected to modulate the extent of IFN inhibition. Here, we studied the impact of IFN on various aspects of HIV replication in primary T lymphocytes. We confirm the potent effect of IFN on Gag p24 production in supernatants. Interestingly, IFN had a more limited effect on HIV spread, measured as the appearance of Gag-expressing cells. Primary isolates displayed similar differences in the inhibition of p24 release and virus spread. Virus emergence was the consequence of suboptimal inhibition of HIV replication and was not due to the selection of resistant variants. Cell-to-cell HIV transfer, a potent means of virus replication, was less sensitive to IFN than infection by cell-free virions. These results suggest that IFN are less active in cell cultures than initially thought. They help explain the incomplete protection by naturally secreted IFN during HIV infection and the unsatisfactory outcome of IFN treatment in HIV-infected patients.

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