scholarly journals Could Interleukin-33 (IL-33) Govern the Outcome of an Equine Influenza Virus Infection? Learning from Other Species

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2519
Author(s):  
Christoforos Rozario ◽  
Luis Martínez-Sobrido ◽  
Henry J. McSorley ◽  
Caroline Chauché
Keyword(s):  
Immune Responses ◽  
Disease Severity ◽  
Influenza A ◽  
Bacterial Infections ◽  
Influenza Virus Infection ◽  
Airway Epithelial Cells ◽  
Respiratory Pathogens ◽  
Equine Influenza Virus ◽  
Interleukin 33 ◽  
Host Immune Responses

Influenza A viruses (IAVs) are important respiratory pathogens of horses and humans. Infected individuals develop typical respiratory disorders associated with the death of airway epithelial cells (AECs) in infected areas. Virulence and risk of secondary bacterial infections vary among IAV strains. The IAV non-structural proteins, NS1, PB1-F2, and PA-X are important virulence factors controlling AEC death and host immune responses to viral and bacterial infection. Polymorphism in these proteins impacts their function. Evidence from human and mouse studies indicates that upon IAV infection, the manner of AEC death impacts disease severity. Indeed, while apoptosis is considered anti-inflammatory, necrosis is thought to cause pulmonary damage with the release of damage-associated molecular patterns (DAMPs), such as interleukin-33 (IL-33). IL-33 is a potent inflammatory mediator released by necrotic cells, playing a crucial role in anti-viral and anti-bacterial immunity. Here, we discuss studies in human and murine models which investigate how viral determinants and host immune responses control AEC death and subsequent lung IL-33 release, impacting IAV disease severity. Confirming such data in horses and improving our understanding of early immunologic responses initiated by AEC death during IAV infection will better inform the development of novel therapeutic or vaccine strategies designed to protect life-long lung health in horses and humans, following a One Health approach.

Impact of influenza virus during pregnancy: from disease severity to vaccine efficacy

2020 ◽  
Vol 15 (7) ◽  
pp. 441-453
Author(s):  
Ana Vazquez-Pagan ◽  
Rebekah Honce ◽  
Stacey Schultz-Cherry
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Immune Responses ◽  
Pregnant Women ◽  
Disease Severity ◽  
Influenza A ◽  
Antiviral Treatment ◽  
Influenza Virus Infection ◽  
Severe Influenza ◽  
The Impact

Pregnant women are among the individuals at the highest risk for severe influenza virus infection. Infection of the mother during pregnancy increases the probability of adverse fetal outcomes such as small for gestational age, preterm birth and fetal death. Animal models of syngeneic and allogeneic mating can recapitulate the increased disease severity observed in pregnant women and are used to define the mechanism(s) of that increased severity. This review focuses on influenza A virus pathogenesis, the unique immunological landscape during pregnancy, the impact of maternal influenza virus infection on the fetus and the immune responses at the maternal–fetal interface. Finally, we summarize the importance of immunization and antiviral treatment in this population and highlight issues that warrant further investigation.

scholarly journals A TLR5 mono-agonist restores inhibited immune responses to Streptococcus pneumoniae during influenza virus infection in human monocytes

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258261
Author(s):  
Paula T. Maguire ◽  
Sinéad T. Loughran ◽  
Ruth Harvey ◽  
Patricia A. Johnson
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Influenza A ◽  
Bacterial Infections ◽  
Influenza Virus Infection ◽  
Human Monocytes ◽  
Streptococcus Pneumonia ◽  
Th17 Response ◽  
Tlr Agonist ◽  
New Treatments

Influenza A virus (IAV) predisposes individuals to often more severe secondary bacterial infections with Streptococcus pneumonia (S. pneumoniae). The outcomes of these infections may be made worse with the increase in antimicrobial resistance and a lack of new treatments to combat this. Th17 responses are crucial in clearing S. pneumoniae from the lung. We previously demonstrated that early IAV infection of human monocytes significantly reduced levels of S. pneumoniae-driven cytokines involved in the Th17 response. Here, we have further identified that IAV targets specific TLRs (TLR2, TLR4, TLR9) involved in sensing S. pneumoniae infection resulting, in a reduction in TLR agonist-induced IL-23 and TGF-β. The effect of IAV is more profound on the TLR2 and TLR9 pathways. We have established that IAV-mediated inhibition of TLR9-induction is related to a downregulation of RORC, a Th17 specific transcription factor. Other studies using mouse models demonstrated that TLR5 agonism improved the efficacy of antibiotics in the treatment of IAV/S. pneumoniae co-infections. Therefore, we investigated if TLR5 agonism could restore inhibited Th17 responses in human monocytes. Levels of pneumococcus-driven cytokines, which had previously been inhibited by IAV were not reduced in the presence of the TLR5 mono-agonist, suggesting that such treatment may overcome IAV inhibition of Th17 responses. The importance of our research is in demonstrating the IAV directly targets S. pneumoniae-associated TLR pathways. Additionally, the IAV-inhibition of Th17 responses can be restored by TLR5 agonism, which indicates that there may be a different Th17 signalling pathway which is not affected by IAV infection.

scholarly journals Impact of Influenza A Virus Shutoff Proteins on Host Immune Responses

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 629
Author(s):  
Megan M. Dunagan ◽  
Kala Hardy ◽  
Toru Takimoto
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Influenza A Virus ◽  
Influenza A ◽  
Human Populations ◽  
Lymphocyte Migration ◽  
Host Immune Responses ◽  
Mhc Molecules ◽  
The Impact

Influenza A virus (IAV) is a significant human pathogen that causes seasonal epidemics. Although various types of vaccines are available, IAVs still circulate among human populations, possibly due to their ability to circumvent host immune responses. IAV expresses two host shutoff proteins, PA-X and NS1, which antagonize the host innate immune response. By transcriptomic analysis, we previously showed that PA-X is a major contributor for general shutoff, while shutoff active NS1 specifically inhibits the expression of host cytokines, MHC molecules, and genes involved in innate immunity in cultured human cells. So far, the impact of these shutoff proteins in the acquired immune response in vivo has not been determined in detail. In this study, we analyzed the effects of PA-X and NS1 shutoff activities on immune response using recombinant influenza A/California/04/2009 viruses containing mutations affecting the expression of shutoff active PA-X and NS1 in a mouse model. Our data indicate that the virus without shutoff activities induced the strongest T and B cell responses. Both PA-X and NS1 reduced host immune responses, but shutoff active NS1 most effectively suppressed lymphocyte migration to the lungs, antibody production, and the generation of IAV specific CD4+ and CD8+ T cells. NS1 also prevented the generation of protective immunity against a heterologous virus challenge. These data indicate that shutoff active NS1 plays a major role in suppressing host immune responses against IAV infection.

scholarly journals Regulation of Early Host Immune Responses Shapes the Pathogenicity of Avian Influenza A Virus

2019 ◽  
Vol 10 ◽  
Author(s):  
Jiya Sun ◽  
Jingfeng Wang ◽  
Xuye Yuan ◽  
Xiangwei Wu ◽  
Tianqi Sui ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Immune Responses ◽  
Influenza A Virus ◽  
Influenza A ◽  
Host Immune Responses ◽  
Avian Influenza A Virus

scholarly journals Replicating Single-Cycle Adenovirus Vectors Generate Amplified Influenza Vaccine Responses

2016 ◽  
Vol 91 (2) ◽  
Author(s):  
Catherine M. Crosby ◽  
William E. Matchett ◽  
Stephanie S. Anguiano-Zarate ◽  
Christopher A. Parks ◽  
Eric A. Weaver ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Influenza A ◽  
Viral Vectors ◽  
Rhesus Macaques ◽  
Influenza Virus Infection ◽  
Single Cycle ◽  
Syrian Hamsters ◽  
Hemagglutinin Protein

ABSTRACT Head-to-head comparisons of conventional influenza vaccines with adenovirus (Ad) gene-based vaccines demonstrated that these viral vectors can mediate more potent protection against influenza virus infection in animal models. In most cases, Ad vaccines are engineered to be replication-defective (RD-Ad) vectors. In contrast, replication-competent Ad (RC-Ad) vaccines are markedly more potent but risk causing adenovirus diseases in vaccine recipients and health care workers. To harness antigen gene replication but avoid production of infectious virions, we developed “single-cycle” adenovirus (SC-Ad) vectors. Previous work demonstrated that SC-Ads amplify transgene expression 100-fold and produce markedly stronger and more persistent immune responses than RD-Ad vectors in Syrian hamsters and rhesus macaques. To test them as potential vaccines, we engineered RD and SC versions of adenovirus serotype 6 (Ad6) to express the hemagglutinin (HA) gene from influenza A/PR/8/34 virus. We show here that it takes approximately 33 times less SC-Ad6 than RD-Ad6 to produce equal amounts of HA antigen in vitro. SC-Ad produced markedly higher HA binding and hemagglutination inhibition (HAI) titers than RD-Ad in Syrian hamsters. SC-Ad-vaccinated cotton rats had markedly lower influenza titers than RD-Ad-vaccinated animals after challenge with influenza A/PR/8/34 virus. These data suggest that SC-Ads may be more potent vaccine platforms than conventional RD-Ad vectors and may have utility as “needle-free” mucosal vaccines. IMPORTANCE Most adenovirus vaccines that are being tested are replication-defective adenoviruses (RD-Ads). This work describes testing newer single-cycle adenovirus (SC-Ad) vectors that replicate transgenes to amplify protein production and immune responses. We show that SC-Ads generate markedly more influenza virus hemagglutinin protein and require substantially less vector to generate the same immune responses as RD-Ad vectors. SC-Ads therefore hold promise to be more potent vectors and vaccines than current RD-Ad vectors.

Contribution of innate immune cells to pathogenesis of severe influenza virus infection

2017 ◽  
Vol 131 (4) ◽  
pp. 269-283 ◽  
Author(s):  
Suzanne L. Cole ◽  
Ling-Pei Ho
Keyword(s):  
Immune Response ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Respiratory Illness ◽  
Airway Epithelial Cells ◽  
Innate Immune ◽  
Airway Epithelial ◽  
Cell Type ◽  
Influenza A Viruses ◽  
Effector Cells

Influenza A viruses (IAVs) cause respiratory illness of varying severity based on the virus strains, host predisposition and pre-existing immunity. Ultimately, outcome and recovery from infection rely on an effective immune response comprising both innate and adaptive components. The innate immune response provides the first line of defence and is crucial to the outcome of infection. Airway epithelial cells are the first cell type to encounter the virus in the lungs, providing antiviral and chemotactic molecules that shape the ensuing immune response by rapidly recruiting innate effector cells such as NK cells, monocytes and neutrophils. Each cell type has unique mechanisms to combat virus-infected cells and limit viral replication, however their actions may also lead to pathology. This review focuses how innate cells contribute to protection and pathology, and provides evidence for their involvement in immune pathology in IAV infections.

scholarly journals Interferon mediated prophylactic protection against respiratory viruses conferred by a prototype live attenuated influenza virus vaccine lacking non-structural protein 1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raveen Rathnasinghe ◽  
Mirella Salvatore ◽  
Hongyong Zheng ◽  
Sonia Jangra ◽  
Thomas Kehrer ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Vaccine ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Influenza Virus Vaccine ◽  
Influenza Viruses ◽  
Type I ◽  
Respiratory Pathogens ◽  
Structural Protein ◽  
Human Influenza Virus

AbstractThe influenza A non-structural protein 1 (NS1) is known for its ability to hinder the synthesis of type I interferon (IFN) during viral infection. Influenza viruses lacking NS1 (ΔNS1) are under clinical development as live attenuated human influenza virus vaccines and induce potent influenza virus-specific humoral and cellular adaptive immune responses. Attenuation of ΔNS1 influenza viruses is due to their high IFN inducing properties, that limit their replication in vivo. This study demonstrates that pre-treatment with a ΔNS1 virus results in an antiviral state which prevents subsequent replication of homologous and heterologous viruses, preventing disease from virus respiratory pathogens, including SARS-CoV-2. Our studies suggest that ΔNS1 influenza viruses could be used for the prophylaxis of influenza, SARS-CoV-2 and other human respiratory viral infections, and that an influenza virus vaccine based on ΔNS1 live attenuated viruses would confer broad protection against influenza virus infection from the moment of administration, first by non-specific innate immune induction, followed by specific adaptive immunity.

scholarly journals Citrobacter amalonaticus Inhibits the Growth of Citrobacter rodentium in the Gut Lumen

mBio ◽  
2021 ◽  
Author(s):  
Caroline Mullineaux-Sanders ◽  
Danielle Carson ◽  
Eve G. D. Hopkins ◽  
Izabela Glegola-Madejska ◽  
Alejandra Escobar-Zepeda ◽  
...  
Keyword(s):  
Immune Responses ◽  
Virulence Factors ◽  
Bacterial Infections ◽  
Citrobacter Rodentium ◽  
Colonization Resistance ◽  
Host Immune Responses ◽  
Citrobacter Amalonaticus

Gut bacterial infections involve three-way interactions between virulence factors, the host immune responses, and the microbiome. While the microbiome erects colonization resistance barriers, pathogens employ virulence factors to overcome them.

scholarly journals MCMV-based vaccine vectors expressing full-length viral proteins provide long-term humoral immune protection upon a single-shot vaccination

2022 ◽  
Author(s):  
Yeonsu Kim ◽  
Xiaoyan Zheng ◽  
Kathrin Eschke ◽  
M. Zeeshan Chaudhry ◽  
Federico Bertoglio ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Influenza A ◽  
High Morbidity ◽  
Single Shot ◽  
Respiratory Pathogens ◽  
Antigenic Peptides ◽  
Immune Protection ◽  
Vaccine Vectors

AbstractGlobal pandemics caused by influenza or coronaviruses cause severe disruptions to public health and lead to high morbidity and mortality. There remains a medical need for vaccines against these pathogens. CMV (cytomegalovirus) is a β-herpesvirus that induces uniquely robust immune responses in which remarkably large populations of antigen-specific CD8+ T cells are maintained for a lifetime. Hence, CMV has been proposed and investigated as a novel vaccine vector for expressing antigenic peptides or proteins to elicit protective cellular immune responses against numerous pathogens. We generated two recombinant murine CMV (MCMV) vaccine vectors expressing hemagglutinin (HA) of influenza A virus (MCMVHA) or the spike protein of severe acute respiratory syndrome coronavirus 2 (MCMVS). A single injection of MCMVs expressing either viral protein induced potent neutralizing antibody responses, which strengthened over time. Importantly, MCMVHA-vaccinated mice were protected from illness following challenge with the influenza virus, and we excluded that this protection was due to the effects of memory T cells. Conclusively, we show here that MCMV vectors induce not only long-term cellular immunity but also humoral responses that provide long-term immune protection against clinically relevant respiratory pathogens.

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