scholarly journals Exogenous Interleukin-33 Contributes to Protective Immunity via Cytotoxic T-Cell Priming against Mucosal Influenza Viral Infection

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 840 ◽  
Author(s):  
Chae Won Kim ◽  
Hye Jee Yoo ◽  
Jang Hyun Park ◽  
Ji Eun Oh ◽  
Heung Kyu Lee
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
T Cell ◽  
Viral Infections ◽  
Influenza Infection ◽  
Influenza Virus Infection ◽  
Respiratory Illness ◽  
Cytotoxic T Cell ◽  
Antiviral Immune Response ◽  
Cytotoxic T Cell Responses

Influenza is an infectious respiratory illness caused by the influenza virus. Though vaccines against influenza exist, they have limited efficacy. To additionally develop effective treatments, there is a need to study the mechanisms of host defenses from influenza viral infections. To date, the mechanism by which interleukin (IL)-33 modulates the antiviral immune response post-influenza infection is unclear. In this study, we demonstrate that exogenous IL-33 enhanced antiviral protection against influenza virus infection. Exogenous IL-33 induced the recruitment of dendritic cells, increased the secretion of pro-inflammatory cytokine IL-12, and promoted cytotoxic T-cell responses in the local microenvironment. Thus, our findings suggest a role of exogenous IL-33 in the antiviral immune response against influenza infection.

scholarly journals Flow Cytometric and Cytokine ELISpot Approaches To Characterize the Cell-Mediated Immune Response in Ferrets following Influenza Virus Infection

2016 ◽  
Vol 90 (17) ◽  
pp. 7991-8004 ◽  
Author(s):  
Anthony DiPiazza ◽  
Katherine Richards ◽  
Frances Batarse ◽  
Laura Lockard ◽  
Hui Zeng ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Virus Infection ◽  
Influenza Infection ◽  
Influenza Virus Infection ◽  
Flow Cytometric ◽  
Cell Mediated Immune Response ◽  
Mhc Locus

ABSTRACTInfluenza virus infections represent a significant socioeconomic and public health burden worldwide. Although ferrets are considered by many to be ideal for modeling human responses to influenza infection and vaccination, efforts to understand the cellular immune response have been severely hampered by a paucity of standardized procedures and reagents. In this study, we developed flow cytometric and T cell enzyme-linked immunosorbent spot (ELISpot) approaches to characterize the leukocyte composition and antigen-specific T cell response within key lymphoid tissues following influenza virus infection in ferrets. Through a newly designed and implemented set of serological reagents, we used multiparameter flow cytometry to directly quantify the frequency of CD4+and CD8+T cells, Ig+B cells, CD11b+myeloid-derived cells, and major histocompatibility complex (MHC) class II-positive antigen-presenting cells (APCs) both prior to and after intranasal infection with A/California/04/09 (H1N1). We found that the leukocyte composition was altered at 10 days postinfection, with notable gains in the frequency of T cells and myeloid cells within the draining lymph node. Furthermore, these studies revealed that the antigen specificity of influenza virus-reactive CD4 and CD8 T cells was very broad, with recognition of the viral HA, NA, M1, NS1, and NP proteins, and that total reactivity to influenza virus postinfection represented approximately 0.1% of the circulating peripheral blood mononuclear cells (PBMC). Finally, we observed distinct patterns of reactivity between individual animals, suggesting heterogeneity at the MHC locus in ferrets within commercial populations, a finding of considerable interest in efforts to move the ferret model forward for influenza vaccine and challenge studies.IMPORTANCEFerrets are an ideal animal model to study transmission, diseases, and vaccine efficacies of respiratory viruses because of their close anatomical and physiological resemblances to humans. However, a lack of reagents has limited our understanding of the cell-mediated immune response following infection and vaccination. In this study, we used cross-reactive and ferret-specific antibodies to study the leukocyte composition and antigen-specific CD4 and CD8 T cell responses following influenza A/California/04/09 (H1N1) virus infection. These studies revealed strikingly distinct patterns of reactivity between CD4 and CD8 T cells, which were overlaid with differences in protein-specific responses between individual animals. Our results provide a first, in-depth look at the T cell repertoire in response to influenza infection and suggest that there is considerable heterogeneity at the MHC locus, which is akin to that in humans and an area of intense research interest.

scholarly journals Autoimmune neutropenia associated with influenza virus infection in childhood: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ignacio Callejas Caballero ◽  
Marta Illán Ramos ◽  
Arantxa Berzosa Sánchez ◽  
Eduardo Anguita ◽  
José Tomás Ramos Amador
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Viral Infections ◽  
Influenza Infection ◽  
Influenza Virus Infection ◽  
Rapid Test ◽  
Male Infant ◽  
Severe Neutropenia ◽  
Autoimmune Neutropenia ◽  
Benign Condition

Abstract Background Although neutropenia is relatively frequent in infants and children and is mostly a benign condition with a self-limited course, it can lead to life-threatening severe infections. Autoimmune neutropenia is a relatively uncommon hematological disorder characterized by the autoantibody-induced destruction of neutrophils. It is usually triggered by viral infections with very few documented cases after influenza virus. Case presentation An 8-month-old male infant presented at the emergency room with a 5-days history of fever up to 39.7 °C, cough and runny nose. In the blood test performed, severe neutropenia was diagnosed (neutrophils 109/μL). A nasopharyngeal aspirate revealed a positive rapid test for Influenza A. Serum antineutrophil antibodies were determined with positive results. Neutropenia targeted panel showed no mutations. Despite maintenance of severe neutropenia for 9 months the course was uneventful without treatment. Conclusions When severe neutropenia is diagnosed and confirmed, it is essential to rule out some potential etiologies and underlying conditions, since the appropriate subsequent management will depend on it. Although autoimmune neutropenia triggered by viral infections has been widely reported, it has seldom been reported after influenza infection. The benign course of the disease allows a conservative management in most cases.

scholarly journals HLA-linked genetic control of the specicity of human cytotoxic T-cell responses to influenza virus.

1979 ◽  
Vol 149 (3) ◽  
pp. 565-575 ◽  
Author(s):  
S Shaw ◽  
W E Biddison
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
Genetic Control ◽  
Large Family ◽  
T Cell Responses ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Cell Responses ◽  
Cytotoxic T Cell Responses

We have investigated elements of the genetic control of human in vitro cytotoxic T-cell responses to influenza virus-infected autologous cells by studies of a large family. The pattern of virus-immune cytotoxicity among siblings demonstrated T-cell recognition of influenza virus predominantly (greater than 90%) in association with determinants which are coded by genes linked to HLA (P less than 0.0002). Many family members consistently generated cytotoxic activity against influenza predominantly in association with antigens coded by genes of only one of their HLA haplotypes. Such haplotype preferences were consistent among HLA-identical siblings, indicating that the specificity of the T-cell response to influenza virus in association with HLA-A and -B antigens is controlled by genes linked to HLA.

scholarly journals Mouse Models Reveal Role of T-Cytotoxic and T-Reg Cells in Immune Response to Influenza: Implications for Vaccine Design

Viruses ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 52 ◽  
Author(s):  
Stewart Sell ◽  
Karl McKinstry ◽  
Tara Strutt
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Influenza Virus ◽  
Epithelial Cells ◽  
Mouse Models ◽  
Viral Infections ◽  
Influenza Virus Infection ◽  
Bronchial Epithelium ◽  
Cytotoxic Cells ◽  
Type Ii Pneumocytes

Immunopathologic examination of the lungs of mouse models of experimental influenza virus infection provides new insights into the immune response in this disease. First, there is rapidly developing perivascular and peribronchial infiltration of the lung with T-cells. This is followed by invasion of T-cells into the bronchiolar epithelium, and separation of epithelial cells from each other and from the basement membrane leading to defoliation of the bronchial epithelium. The intraepithelial reaction may involve either CD8 or CD4 T-cytotoxic cells and is analogous to a viral exanthema of the skin, such as measles and smallpox, which occur when the immune response against these infections is activated and the infected cells are attacked by T-cytotoxic cells. Then there is formation of B-cell follicles adjacent to bronchi, i.e., induced bronchial associated lymphoid tissue (iBALT). iBALT reacts like the cortex of a lymph node and is a site for a local immune response not only to the original viral infection, but also related viral infections (heterologous immunity). Proliferation of Type II pneumocytes and/or terminal bronchial epithelial cells may extend into the adjacent lung leading to large zones filled with tumor-like epithelial cells. The effective killing of influenza virus infected epithelial cells by T-cytotoxic cells and induction of iBALT suggests that adding the induction of these components might greatly increase the efficacy of influenza vaccination.

scholarly journals Modelling The Effect of MUC1 on Influenza Virus Infection Kinetics and Macrophage Dynamics

2021 ◽  
Author(s):  
Ke Li ◽  
Pengxing Cao ◽  
James M. McCaw
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Viral Replication ◽  
Influenza Infection ◽  
Influenza Virus Infection ◽  
Host Immune Response ◽  
Viral Control ◽  
Macrophage Populations ◽  
Influenza Viral Infection

AbstractMUC1 belongs to the family of cell surface (cs-) mucins. Experimental evidence indicates that its presence reduces in vivo influenza viral infection severity. However, the mechanisms by which MUC1 influences viral dynamics and the host immune response are not yet well understood, limiting our ability to predict the efficacy of potential treatments that target MUC1. To address this limitation, we utilize available in vivo kinetic data for both virus and macrophage populations in wildtype and MUC1 knockout mice. We apply two mathematical models of within-host influenza dynamics to this data. The models differ in how they categorise the mechanisms of viral control. Both models provide evidence that MUC1 reduces the susceptibility of epithelial cells to influenza virus and regulates macrophage recruitment. Furthermore, we predict and compare some key infection-related quantities between the two mice groups. We find that MUC1 significantly reduces the basic reproduction number of viral replication as well as the number of cumulative macrophages but has little impact on the cumulative viral load. Our analyses suggest that the viral replication rate in the early stages of infection influences the kinetics of the host immune response, with consequences for infection outcomes, such as severity. We also show that MUC1 plays a strong anti-inflammatory role in the regulation of the host immune response. This study improves our understanding of the dynamic role of MUC1 against influenza infection and may support the development of novel antiviral treatments and immunomodulators that target MUC1.

scholarly journals Local IL-4 Expression in the Lung Reduces Pulmonary Influenza-Virus-Specific Secondary Cytotoxic T Cell Responses

Virology ◽  
2000 ◽  
Vol 269 (1) ◽  
pp. 66-77 ◽  
Author(s):  
Adrian Bot ◽  
Andreas Holz ◽  
Urs Christen ◽  
Tom Wolfe ◽  
Angela Temann ◽  
...  
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
T Cell Responses ◽  
Cytotoxic T Cell ◽  
Cell Responses ◽  
Cytotoxic T Cell Responses

scholarly journals Inhibition of indoleamine 2,3-dioxygenase enhances the T-cell response to influenza virus infection

2013 ◽  
Vol 94 (7) ◽  
pp. 1451-1461 ◽  
Author(s):  
Julie M. Fox ◽  
Leo K. Sage ◽  
Lei Huang ◽  
James Barber ◽  
Kimberly D. Klonowski ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Virus Infection ◽  
Cell Response ◽  
Influenza Virus Infection ◽  
T Cell Response ◽  
Th17 Response ◽  
Indoleamine 2,3 Dioxygenase

Influenza infection induces an increase in the level of indoleamine 2,3-dioxygenase (IDO) activity in the lung parenchyma. IDO is the first and rate-limiting step in the kynurenine pathway where tryptophan is reduced to kynurenine and other metabolites. The depletion of tryptophan, and production of associated metabolites, attenuates the immune response to infection. The impact of IDO on the primary immune response to influenza virus infection was determined using the IDO inhibitor 1-methyl-d,l-tryptophan (1MT). C57BL/6 mice treated with 1MT and infected with A/HKx31 influenza virus had increased numbers of activated and functional CD4+ T-cells, influenza-specific CD8+ T-cells and effector memory cells in the lung. Inhibition of IDO increased the Th1 response in CD4+ T-cells as well as enhanced the Th17 response. These studies show that inhibition of IDO engenders a more robust T-cell response to influenza virus, and suggests an approach for enhancing the immune response to influenza vaccination by facilitating increased influenza-specific T-cell response.

scholarly journals Designing a multi-epitope vaccine candidate to combat MERS-CoV by employing an immunoinformatics approach

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shafi Mahmud ◽  
Md. Oliullah Rafi ◽  
Gobindo Kumar Paul ◽  
Maria Meha Promi ◽  
Mst. Sharmin Sultana Shimu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Viral Infections ◽  
Vaccine Candidate ◽  
Cytotoxic T Cell ◽  
Binding Affinities ◽  
Spike Glycoprotein ◽  
Epitope Vaccine ◽  
Suitable Target ◽  
Antigenic Vaccine

AbstractCurrently, no approved vaccine is available against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes severe respiratory disease. The spike glycoprotein is typically considered a suitable target for MERS-CoV vaccine candidates. A computational strategy can be used to design an antigenic vaccine against a pathogen. Therefore, we used immunoinformatics and computational approaches to design a multi-epitope vaccine that targets the spike glycoprotein of MERS-CoV. After using numerous immunoinformatics tools and applying several immune filters, a poly-epitope vaccine was constructed comprising cytotoxic T-cell lymphocyte (CTL)-, helper T-cell lymphocyte (HTL)-, and interferon-gamma (IFN-γ)-inducing epitopes. In addition, various physicochemical, allergenic, and antigenic profiles were evaluated to confirm the immunogenicity and safety of the vaccine. Molecular interactions, binding affinities, and the thermodynamic stability of the vaccine were examined through molecular docking and dynamic simulation approaches, during which we identified a stable and strong interaction with Toll-like receptors (TLRs). In silico immune simulations were performed to assess the immune-response triggering capabilities of the vaccine. This computational analysis suggested that the proposed vaccine candidate would be structurally stable and capable of generating an effective immune response to combat viral infections; however, experimental evaluations remain necessary to verify the exact safety and immunogenicity profile of this vaccine.

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