A critical role of IL-17 in modulating the B-cell response during H5N1 influenza virus infection

Abstract Background Neutrophil (Nϕ) is of the most abundant number in human immune system. During acute influenza virus infection, Nϕs are already active in the early phase of inflammation-a time in which clinical biopsy or autopsy material is not readily available. However, the role of Nϕ in virus infection is not well understood. Here, we studied the role of Nϕ in host defense during influenza A virus infection, specifically assessing if it contributes to the differential pathogenesis in H5N1 disease. Methods Nϕs were freshly isolated from healthy volunteers and subjected to direct influenza H1N1 and H5N1 virus infection in vitro . The ability of the naïve Nϕs to infiltrate from the basolateral to the apical phase of the influenza virus infected alveolar epithelium was assessed. The viral replication, innate immune responses and Neutrophil extracellular trap (NET) formation of Nϕs upon influenza virus infection were evaluated. Results Our results demonstrated that influenza virus infected alveolar epithelium allowed more Nϕs transmigration. Significantly more Nϕs migrated across the H5N1 influenza virus infected the epithelium than the counterpart infected by the seasonal influenza H1N1 virus infected. Nϕs were equally susceptible to H5N1 and H1N1 virus infection with similar viral gene transcription. Productive replication was observed in H5N1 infected Nϕs. Both H5N1 and H1N1 infected Nϕs induced cytokines and chemokines including TNF-α, IFN-β, CXCL10, MIP-1α and IL-8. This inferred a more intense inflammatory response posed by H5N1 than H1N1 virus. Strikingly, NADPH oxidase-independent NET formation was observed in H1N1 infected Nϕs at 6 hpi while no NET formation was observed upon H5N1 infection. Conclusion Our data is the first to demonstrate that NET formation is abrogated in H5N1 influenza virus infection. Its contribution to the differential severity of H5N1 disease requires further investigation.

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Host DNA released by NETosis in neutrophils exposed to seasonal H1N1 and highly pathogenic H5N1 influenza viruses

10.21203/rs.2.24164/v2 ◽

2020 ◽

Author(s):

Louisa L.Y. Chan ◽

John M. Nicholls ◽

J.S. Malik Peiris ◽

Yu Lung Lau ◽

Michael C.W. Chan ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Gene Transcription ◽

H1n1 Virus ◽

Influenza Virus Infection ◽

Alveolar Epithelium ◽

H5n1 Influenza Virus ◽

H5n1 Influenza ◽

Influenza H1n1

Abstract Background: Neutrophil is of the most abundant number in human immune system. During acute influenza virus infection, neutrophils are already active in the early phase of inflammation-a time in which clinical biopsy or autopsy material is not readily available. However, the role of neutrophil in virus infection is not well understood. Here, we studied the role of neutrophil in host defense during influenza A virus infection, specifically assessing if it contributes to the differential pathogenesis in H5N1 disease. Methods: Neutrophils were freshly isolated from healthy volunteers and subjected to direct influenza H1N1 and H5N1 virus infection in vitro. The ability of the naïve neutrophils to infiltrate from the basolateral to the apical phase of the influenza virus infected alveolar epithelium was assessed. The viral replication, innate immune responses and Neutrophil extracellular trap (NET) formation of neutrophils upon influenza virus infection were evaluated. Results: Our results demonstrated that influenza virus infected alveolar epithelium allowed more neutrophils transmigration. Significantly more neutrophils migrated across the H5N1 influenza virus infected the epithelium than the counterpart infected by the seasonal influenza H1N1 virus infected. Neutrophils were equally susceptible to H5N1 and H1N1 virus infection with similar viral gene transcription. Productive replication was observed in H5N1 infected neutrophils. H5N1 induced higher cytokine and chemokine gene transcription than H1N1 infected neutrophils, including TNF-α, IFN-β, CXCL10, MIP-1α and IL-8. This inferred a more intense inflammatory response posed by H5N1 than H1N1 virus. Strikingly, NADPH oxidase-independent NET formation was only observed in H1N1 infected neutrophils at 6 hpi while no NET formation was observed upon H5N1 infection.Conclusion: Our data is the first to demonstrate that NET formation is abrogated in H5N1 influenza virus infection and might contribute to the severity of H5N1 disease.

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Influenza Virus Infection Causes Global Respiratory Tract B Cell Response Modulation via Innate Immune Signals

The Journal of Immunology ◽

10.4049/jimmunol.178.3.1457 ◽

2007 ◽

Vol 178 (3) ◽

pp. 1457-1467 ◽

Cited By ~ 49

Author(s):

W. L. William Chang ◽

Elizabeth S. Coro ◽

Friederike C. Rau ◽

Yuanyuan Xiao ◽

David J. Erle ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Respiratory Tract ◽

B Cell ◽

Cell Response ◽

Influenza Virus Infection ◽

Innate Immune ◽

Response Modulation ◽

B Cell Response

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Host DNA released by NETosis in neutrophils exposed to seasonal H1N1 and highly pathogenic H5N1 influenza viruses

Respiratory Research ◽

10.1186/s12931-020-01425-w ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 1

Author(s):

Louisa L. Y. Chan ◽

John M. Nicholls ◽

J. S. Malik Peiris ◽

Yu Lung Lau ◽

Michael C. W. Chan ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Gene Transcription ◽

H1n1 Virus ◽

Influenza Virus Infection ◽

Alveolar Epithelium ◽

H5n1 Influenza Virus ◽

H5n1 Influenza ◽

Influenza H1n1

Abstract Background Neutrophil is of the most abundant number in human immune system. During acute influenza virus infection, neutrophils are already active in the early phase of inflammation - a time in which clinical biopsy or autopsy material is not readily available. However, the role of neutrophil in virus infection is not well understood. Here, we studied the role of neutrophil in host defense during influenza A virus infection, specifically assessing if it contributes to the differential pathogenesis in H5N1 disease. Methods Neutrophils were freshly isolated from healthy volunteers and subjected to direct influenza H1N1 and H5N1 virus infection in vitro. The ability of the naïve neutrophils to infiltrate from the basolateral to the apical phase of the influenza virus infected alveolar epithelium was assessed. The viral replication, innate immune responses and Neutrophil extracellular trap (NET) formation of neutrophils upon influenza virus infection were evaluated. Results Our results demonstrated that influenza virus infected alveolar epithelium allowed neutrophil transmigration. Significantly more neutrophils migrated across the H5N1 influenza virus infected the epithelium than the counterpart infected by the seasonal influenza H1N1 virus infected. Neutrophils were equally susceptible to H5N1 and H1N1 virus infection with similar viral gene transcription. Productive replication was observed in H5N1 infected neutrophils. H5N1 induced higher cytokine and chemokine gene transcription than H1N1 infected neutrophils, including TNF-α, IFN-β, CXCL10, MIP-1α and IL-8. This inferred a more intense inflammatory response posed by H5N1 than H1N1 virus. Strikingly, NADPH oxidase-independent NET formation was only observed in H1N1 infected neutrophils at 6 hpi while no NET formation was observed upon H5N1 infection. Conclusion Our data is the first to demonstrate that NET formation is abrogated in H5N1 influenza virus infection and might contribute to the severity of H5N1 disease.

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Role of Hypercytokinemia in NF-κB p50-Deficient Mice after H5N1 Influenza A Virus Infection

Journal of Virology ◽

10.1128/jvi.01071-08 ◽

2008 ◽

Vol 82 (22) ◽

pp. 11461-11466 ◽

Cited By ~ 36

Author(s):

Karoline Droebner ◽

Sarah Julia Reiling ◽

Oliver Planz

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Transgenic Mouse ◽

Proinflammatory Cytokines ◽

Influenza A ◽

Influenza Virus Infection ◽

H5n1 Influenza Virus ◽

Cytokines And Chemokines ◽

H5n1 Influenza

ABSTRACT During H5N1 influenza virus infection, proinflammatory cytokines are markedly elevated in the lungs of infected hosts. The significance of this dysregulated cytokine response in H5N1-mediated pathogenesis remains to be determined. To investigate the influence of hypercytokinemia, or “cytokine storm,” a transgenic mouse technology was used. The classical NF-κB pathway regulates the induction of most proinflammatory cytokines. Deletion of the p50 subunit leads to a markedly reduced expression of the NF-κB-regulated cytokines and chemokines. Here we show that H5N1 influenza virus infection of this transgenic mouse model resulted in a lack of hypercytokinemia but not in altered pathogenesis.

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Lethal Coinfection of Influenza Virus and Streptococcus pneumoniae Lowers Antibody Response to Influenza Virus in Lung and Reduces Numbers of Germinal Center B Cells, T Follicular Helper Cells, and Plasma Cells in Mediastinal Lymph Node

Journal of Virology ◽

10.1128/jvi.02455-14 ◽

2014 ◽

Vol 89 (4) ◽

pp. 2013-2023 ◽

Cited By ~ 11

Author(s):

Yuet Wu ◽

Wenwei Tu ◽

Kwok-Tai Lam ◽

Kin-Hung Chow ◽

Pak-Leung Ho ◽

...

Keyword(s):

Influenza Virus ◽

B Cells ◽

Virus Infection ◽

B Cell ◽

Cell Response ◽

Plasma Cells ◽

Pneumococcal Infection ◽

Influenza Virus Infection ◽

Follicular Helper ◽

B Cell Response

ABSTRACTSecondaryStreptococcus pneumoniaeinfection after influenza is a significant clinical complication resulting in morbidity and sometimes mortality. Prior influenza virus infection has been demonstrated to impair the macrophage and neutrophil response to the subsequent pneumococcal infection. In contrast, how a secondary pneumococcal infection after influenza can affect the adaptive immune response to the initial influenza virus infection is less well understood. Therefore, this study focuses on how secondary pneumococcal infection after influenza may impact the humoral immune response to the initial influenza virus infection in a lethal coinfection mouse model. Compared to mice infected with influenza virus alone, mice coinfected with influenza virus followed by pneumococcus had significant body weight loss and 100% mortality. In the lung, lethal coinfection significantly increased virus titers and bacterial cell counts and decreased the level of virus-specific IgG, IgM, and IgA, as well as the number of B cells, CD4 T cells, and plasma cells. Lethal coinfection significantly reduced the size and weight of spleen, as well as the number of B cells along the follicular developmental lineage. In mediastinal lymph nodes, lethal coinfection significantly decreased germinal center B cells, T follicular helper cells, and plasma cells. Adoptive transfer of influenza virus-specific immune serum to coinfected mice improved survival, suggesting the protective functions of anti-influenza virus antibodies. In conclusion, coinfection reduced the B cell response to influenza virus. This study helps us to understand the modulation of the B cell response to influenza virus during a lethal coinfection.IMPORTANCESecondary pneumococcal infection after influenza virus infection is an important clinical issue that often results in excess mortality. Since antibodies are key mediators of protection, this study aims to examine the antibody response to influenza virus and demonstrates that lethal coinfection reduced the B cell response to influenza virus. This study helps to highlight the complexity of the modulation of the B cell response in the context of coinfection.

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