scholarly journals Interleukin-22 (IL-22) Production by Pulmonary Natural Killer Cells and the Potential Role of IL-22 during Primary Influenza Virus Infection

2010 ◽  
Vol 84 (15) ◽  
pp. 7750-7759 ◽  
Author(s):  
Hailong Guo ◽  
David J. Topham
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Nk Cells ◽  
Viral Infections ◽  
Tissue Injury ◽  
Influenza Virus Infection ◽  
Interleukin 22 ◽  
Virus Clearance ◽  
Ifn Γ

ABSTRACT We set out to test the hypothesis that interleukin-22 (IL-22), a cytokine crucial for epithelial cell homeostasis and recovery from tissue injury, would be protective during influenza virus infection. Recent studies have identified phenotypically and functionally unique intestinal NK cells capable of producing the cytokine IL-22. Unlike gut NK cells that produce IL-22, the surface phenotypes of lung NK cells were similar to those of spleen NK cells and were characteristically mature. With mitogen stimulation, both single and double IL-22- and gamma interferon (IFN-γ)-producing lung NK cells were detected. However, only the IL-22+ IFN-γ− lung NK subset was observed after stimulation with IL-23. IL-23 receptor (IL-23R) blocking dramatically inhibited IL-22 production, but not IFN-γ production. Furthermore, we found that NK1.1+ or CD27− lung NK cells were the primary sources of IL-22. After influenza virus infection, lung NK cells were quickly activated to produce both IFN-γ and IL-22 and had increased cytotoxic potential. The level of IL-22 in the lung tissue declined shortly after infection, gradually returning to the baseline after virus clearance, although the IL-22 gene expression was maintained. Furthermore, depletion of NK cells with or without influenza virus infection reduced the protein level of IL-22 in the lung. Anti-IL-22 neutralization in vivo did not dramatically affect weight loss and survival after virus clearance. Unexpectedly, anti-IL-22-treated mice had reduced virus titers. Our data suggest that during primary respiratory viral infection, IL-22 seems to a play a marginal role for protection, indicating a differential requirement of this cytokine for bacterial and viral infections.

scholarly journals Phenotypic and functional characteristics of a novel influenza hemagglutinin-specific memory NK cell

2021 ◽  
Author(s):  
Jian Zheng ◽  
Liyan Wen ◽  
Hui-Ling Yen ◽  
Ming Liu ◽  
Yinping Liu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Nk Cells ◽  
Nk Cell ◽  
Cell Subset ◽  
Influenza Virus Infection ◽  
Immune Memory ◽  
Influenza Hemagglutinin ◽  
Ifn Γ ◽  
Memory Nk Cells

Immune memory represents the most efficient defense against invasion and transmission of infectious pathogens. In contrast to memory T and B cells, the roles of innate immunity in recall responses remain inconclusive. In this study, we identified a novel mouse spleen NK cell subset expressing NKp46 and NKG2A induced by intranasal influenza virus infection. These memory NK cells specifically recognize N-linked glycosylation sites on influenza hemagglutinin (HA) protein. Different from memory-like NK cells reported previously, these NKp46+NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of IFN-γ response against influenza virus-infected cells, which could be reversed by Pifithrin-μ, a p53-HSP70 signaling inhibitor. During recall responses, splenic NKp46+NKG2A+ NK cells were recruited to infected lung and modulated viral clearance of virus and CD8+ T cell distribution, resulting in improved clinical outcomes. This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response. Importance In this study, we demonstrate a novel HA-specific NKp46+NKG2A+ NK cell subset induced by influenza A virus infection. These memory NK cells show virus-specific decreased cytotoxicity and increased IFN-γ on re-encountering the same influenza virus antigen. In addition, they modulate host recall responses and CD8 T cell distribution, thus bridging the innate immune and adaptive immune responses during influenza virus infection.

scholarly journals Role of Interleukin-12 in Primary Influenza Virus Infection

1998 ◽  
Vol 72 (6) ◽  
pp. 4825-4831 ◽  
Author(s):  
Juanita M. Monteiro ◽  
Catherine Harvey ◽  
Giorgio Trinchieri
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Virus Infection ◽  
Nk Cell ◽  
Influenza Virus Infection ◽  
Interleukin 12 ◽  
Live Virus ◽  
Virus Clearance ◽  
Ifn Γ

ABSTRACT The effect of endogenous interleukin-12 (IL-12) on the influenza virus immune response in BALB/c mice was evaluated. Following primary influenza virus infection, IL-12 mRNA and protein are detected in the lung, with live virus being required for cytokine induction. Endogenous IL-12 contributes to early NK cell-dependent gamma interferon (IFN-γ) production (days 3 and 5) but not late T-cell-dependent IFN-γ secretion (day 7). IL-12 contributes to the inhibition of early virus replication but is not required for virus clearance. IL-12 also modestly contributes to the activation of cytotoxic T lymphocytes. Thus, in this model of experimental influenza virus infection, endogenous IL-12 contributes primarily to the early development and activation of the innate immune response.

scholarly journals Linear polysialoside outperforms dendritic analogs for inhibition of influenza virus infection in vitro and in vivo

Biomaterials ◽  
2017 ◽  
Vol 138 ◽  
pp. 22-34 ◽  
Author(s):  
Sumati Bhatia ◽  
Daniel Lauster ◽  
Markus Bardua ◽  
Kai Ludwig ◽  
Stefano Angioletti-Uberti ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza Virus Infection

scholarly journals Directed Evolution of an Influenza Reporter Virus To Restore Replication and Virulence and Enhance Noninvasive Bioluminescence Imaging in Mice

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Hui Cai ◽  
Meisui Liu ◽  
Charles J. Russell
Keyword(s):  
Gene Expression ◽  
Influenza Virus ◽  
Virus Infection ◽  
Directed Evolution ◽  
Influenza Virus Infection ◽  
Foreign Gene ◽  
Reporter Virus ◽  
Wild Type ◽  
Bioluminescence Signal

ABSTRACTReporter viruses provide a powerful tool to study infection, yet incorporating a nonessential gene often results in virus attenuation and genetic instability. Here, we used directed evolution of a luciferase-expressing pandemic H1N1 (pH1N1) 2009 influenza A virus in mice to restore replication kinetics and virulence, increase the bioluminescence signal, and maintain reporter gene expression. An unadapted pH1N1 virus withNanoLuc luciferaseinserted into the 5′ end of the PA gene segment grew to titers 10-fold less than those of the wild type in MDCK cells and in DBA/2 mice and was less virulent. For 12 rounds, we propagated DBA/2 lung samples with the highest bioluminescence-to-titer ratios. Every three rounds, we comparedin vivoreplication, weight loss, mortality, and bioluminescence. Mouse-adapted virus after 9 rounds (MA-9) had the highest relative bioluminescence signal and had wild-type-like fitness and virulence in DBA/2 mice. Using reverse genetics, we discovered fitness was restored in virus rPB2-MA9/PA-D479N by a combination of PA-D479N and PB2-E158G amino acid mutations andPB2noncoding mutations C1161T and C1977T. rPB2-MA9/PA-D479N has increased mRNA transcription, which helps restore wild-type-like phenotypes in DBA/2 and BALB/c mice. Overall, the results demonstrate that directed evolution that maximizes foreign-gene expression while maintaining genetic stability is an effective method to restore wild-type-likein vivofitness of a reporter virus. Virus rPB2-MA9/PA-D479N is expected to be a useful tool for noninvasive imaging of pH1N1 influenza virus infection and clearance while analyzing virus-host interactions and developing new therapeutics and vaccines.IMPORTANCEInfluenza viruses contribute to 290,000 to 650,000 deaths globally each year. Infection is studied in mice to learn how the virus causes sickness and to develop new drugs and vaccines. During experiments, scientists have needed to euthanize groups of mice at different times to measure the amount of infectious virus in mouse tissues. By inserting a foreign gene that causes infected cells to light up, scientists could see infection spread in living mice. Unfortunately, adding an extra gene not needed by the virus slowed it down and made it weaker. Here, we used a new strategy to restore the fitness and lethality of an influenza reporter virus; we adapted it to mouse lungs and selected for variants that had the greatest light signal. The adapted virus can be used to study influenza virus infection, immunology, and disease in living mice. The strategy can also be used to adapt other viruses.

scholarly journals Multicolor two-photon imaging of in vivo cellular pathophysiology upon influenza virus infection using the two-photon IMPRESS

2020 ◽  
Vol 15 (3) ◽  
pp. 1041-1065 ◽  
Author(s):  
Hiroshi Ueki ◽  
I-Hsuan Wang ◽  
Dongming Zhao ◽  
Matthias Gunzer ◽  
Yoshihiro Kawaoka
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza Virus Infection ◽  
Two Photon ◽  
Photon Imaging ◽  
Two Photon Imaging

scholarly journals Dendritic Cells Targeting Lactobacillus plantarum Strain NC8 with a Surface-Displayed Single-Chain Variable Fragment of CD11c Induce an Antigen-Specific Protective Cellular Immune Response

2019 ◽  
Vol 88 (2) ◽  
Author(s):  
Jing Liu ◽  
Guilian Yang ◽  
Haibin Huang ◽  
Chunwei Shi ◽  
Xing Gao ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Influenza Virus ◽  
Virus Infection ◽  
Lactobacillus Plantarum ◽  
Influenza Virus Infection ◽  
Cell Culture Supernatant ◽  
Single Chain ◽  
Ifn Γ

ABSTRACT Influenza A virus (H1N1) is an acute, highly contagious respiratory virus. The use of lactic acid bacteria (LAB) to deliver mucosal vaccines against influenza virus infection is a research hot spot. In this study, two recombinant Lactobacillus plantarum strains expressing hemagglutinin (HA) alone or coexpressing aCD11c-HA to target HA protein to dendritic cells (DCs) by fusion to an anti-CD11c single-chain antibody (aCD11c) were constructed. The activation of bone marrow dendritic cells (BMDCs) by recombinant strains and the interaction of activated BMDCs and sorted CD4+ or CD8+ T cells were evaluated through flow cytometry in vitro, and cellular supernatants were assessed by using an enzyme-linked immunosorbent assay kit. The results demonstrated that, compared to the HA strain, the aCD11c-HA strain significantly increased the activation of BMDCs and increased the production of CD4+ gamma interferon-positive (IFN-γ+) T cells, CD8+ IFN-γ+ T cells, and IFN-γ in the cell culture supernatant in vitro. Consistent with these results, the aCD11c-HA strain clearly increased the activation and maturation of DCs, the HA-specific responses of CD4+ IFN-γ+ T cells, CD8+ IFN-γ+ T cells, and CD8+ CD107a+ T cells, and the proliferation of T cells in the spleen, finally increasing the levels of specific antibodies and neutralizing antibodies in mice. In addition, the protection of immunized mice was observed after viral infection, as evidenced by improved weight loss, survival, and lung pathology. The adoptive transfer of CD8+ T cells from the aCD11c-HA mice to NOD/Lt-SCID mice resulted in a certain level of protection after influenza virus infection, highlighting the efficacy of the aCD11c targeting strategy.

IFN-γ Treatment at Early Stages of Influenza Virus Infection Protects Mice from Death in a NK Cell-Dependent Manner

2010 ◽  
Vol 30 (6) ◽  
pp. 439-449 ◽  
Author(s):  
Ido D. Weiss ◽  
Ori Wald ◽  
Hanna Wald ◽  
Katia Beider ◽  
Michal Abraham ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Nk Cell ◽  
Influenza Virus Infection ◽  
Dependent Manner ◽  
Early Stages ◽  
Ifn Γ

scholarly journals Influenza Virus Infection Induces Metallothionein Gene Expression in the Mouse Liver and Lung by Overlapping but Distinct Molecular Mechanisms

2001 ◽  
Vol 21 (24) ◽  
pp. 8301-8317 ◽  
Author(s):  
Kalpana Ghoshal ◽  
Sarmila Majumder ◽  
Qin Zhu ◽  
John Hunzeker ◽  
Jharna Datta ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Glucocorticoid Receptor ◽  
Influenza A ◽  
Molecular Mechanisms ◽  
Influenza Virus Infection ◽  
Upper Respiratory Tract ◽  
Response Element ◽  
Induction Process ◽  
Ifn Γ

ABSTRACT Metallothionein I (MT-I) and MT-II have been implicated in the protection of cells against reactive oxygen species (ROS), heavy metals, and a variety of pathological and environmental stressors. Here, we show a robust increase in MT-I/MT-II mRNA level and MT proteins in the livers and lungs of C57BL/6 mice exposed to the influenza A/PR8 virus that infects the upper respiratory tract and lungs. Interleukin-6 (IL-6) had a pronounced effect on the induction of these genes in the liver but not the lung. Treatment of the animals with RU-486, a glucocorticoid receptor antagonist, inhibited induction of MT-I/MT-II in both liver and lung, revealing a direct role of glucocorticoid that is increased upon infection in this induction process. In vivo genomic footprinting (IVGF) analysis demonstrated involvement of almost all metal response elements, major late transcription factor/antioxidant response element (MLTF/ARE), the STAT3 binding site on the MT-I upstream promoter, and the glucocorticoid responsive element (GRE1), located upstream of the MT-II gene, in the induction process in the liver and lung. In the lung, inducible footprinting was also identified at a unique gamma interferon (IFN-γ) response element (γ-IRE) and at Sp1 sites. The mobility shift analysis showed activation of STAT3 and the glucocorticoid receptor in the liver and lung nuclear extracts, which was consistent with the IVGF data. Analysis of the newly synthesized mRNA for cytokines in the infected lung by real-time PCR showed a robust increase in the levels of IL-10 and IFN-γ mRNA that can activate STAT3 and STAT1, respectively. A STAT1-containing complex that binds to the γ-IRE in vitro was activated in the infected lung. No major change in MLTF/ARE DNA binding activity in the liver and lung occurred after infection. These results have demonstrated that MT-I and MT-II can be induced robustly in the liver and lung following experimental influenza virus infection by overlapping but distinct molecular mechanisms.

scholarly journals Main Directions of Effective Influenza Prevention in Modern Conditions

2017 ◽  
Vol 16 (5) ◽  
pp. 80-86
Author(s):  
E. I. Burtseva ◽  
E. A. Mukasheva ◽  
A. G. Rosatkevich
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Risk Analysis ◽  
Viral Infections ◽  
Age Groups ◽  
Influenza Virus Infection ◽  
Mortality Rates ◽  
Influenza Prevention ◽  
Respiratory Viral Infections ◽  
Epidemiological Characteristics

This paper presents the risk analysis of influenza virus infection in different age groups based on the prevalence and mortality rates. The epidemiological characteristics of the influenza virus circulation during postpandemic period are given. Main aspects of specific and non-specific influenza prevention are discussed. The efficacy of the interferon-based medication Grippferon in the prevention of influenza and acute respiratory viral infections (ARVI) is justified.

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