Inflammatory responses in influenza A virus infection

Julkunen, Ilkka; Melén, Krister; Nyqvist, Maria; Pirhonen, Jaana; Sareneva, Timo; Matikainen, Sampsa

doi:10.1016/s0264-410x(00)00275-9

Cited by 237 publications

(205 citation statements)

References 27 publications

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“…Evidence is accumulating to support the idea that apoptosis and inflammation are linked in influenza infection (3,15,35,36,51,52). For example, it has been shown previously that a proinflammatory cytokine, interleukin-8, is secreted upon the induction of apoptosis in bronchiolar epithelial cells by Fas ligation (7,13,15,21).…”

Section: Discussionmentioning

confidence: 97%

Avian Influenza Virus A/HK/483/97(H5N1) NS1 Protein Induces Apoptosis in Human Airway Epithelial Cells

Lam

Tang²,

Yeung³

et al. 2008

J Virol

108

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Avian H5N1 influenza virus causes a remarkably severe disease in humans, with an overall case fatality rate of greater than 50%. Human influenza A viruses induce apoptosis in infected cells, which can lead to organ dysfunction. To verify the role of H5N1-encoded NS1 in inducing apoptosis, the NS1 gene was cloned and expressed in human airway epithelial cells (NCI-H292 cells). The apoptotic events posttransfection were examined by a terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end-labeling assay, flow cytometric measurement of propidium iodide, annexin V staining, and Western blot analyses with antibodies specific for proapoptotic and antiapoptotic proteins. We demonstrated that the expression of H5N1 NS1 protein in NCI-H292 cells was sufficient to induce apoptotic cell death. Western blot analyses also showed that there was prominent cleavage of poly(ADP-ribose) polymerase and activation of caspase-3, caspase-7, and caspase-8 during the NS1-induced apoptosis. The results of caspase inhibitor assays further confirmed the involvement of caspase-dependent pathways in the NS1-induced apoptosis. Interestingly, the ability of H5N1 NS1 protein to induce apoptosis was much enhanced in cells pretreated with Fas ligand (the time posttransfection required to reach >30% apoptosis was reduced from 24 to 6 h). Furthermore, 24 h posttransfection, an increase in Fas ligand mRNA expression of about 5.6-fold was detected in cells transfected with H5N1 NS1. In conclusion, we demonstrated that the NS1 protein encoded by avian influenza A virus H5N1 induced apoptosis in human lung epithelial cells, mainly via the caspase-dependent pathway, which encourages further investigation into the potential for the NS1 protein to be a novel therapeutic target.

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Section: Discussionmentioning

confidence: 97%

Avian Influenza Virus A/HK/483/97(H5N1) NS1 Protein Induces Apoptosis in Human Airway Epithelial Cells

Lam

Tang²,

Yeung³

et al. 2008

J Virol

108

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“…Thus, nonspecific recruitment of pre-established memory T cells to the lung airways appears to be a general feature of inflammation of the lung. However, the underlying mechanism of recruitment remains to be elucidated, although emerging data indicate that monocyte chemoattractant protein 1, RANTES, monocyte IFN-␥-inducible protein, and cytokine-responsive gene 2 may play key roles (28,40,41). We are currently investigating the impact of inflammatory chemokine production on the nonspecific recruitment of memory CD8 ϩ T cells during heterologous infection.…”

Section: Discussionmentioning

confidence: 99%

Nonspecific Recruitment of Memory CD8+ T Cells to the Lung Airways During Respiratory Virus Infections

Ely

Cauley

Roberts

et al. 2003

The Journal of Immunology

129

144

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Previous studies have shown that heterologous viral infections have a significant impact on pre-existing memory T cell populations in secondary lymphoid organs through a combination of cross-reactive and bystander effects. However, the impact of heterologous viral infections on effector/memory T cells in peripheral sites is not well understood. In this study, we have analyzed the impact of a heterologous influenza virus infection on Sendai virus-specific CD8+ effector/memory cells present in the lung airways. The data show a transient increase in the numbers of Sendai virus nucleoprotein 324–332/Kb-specific CD8+ memory T cells in the airways of the influenza-infected mice peaking around day 4 postinfection. Intratracheal transfer studies and 5-bromo-2′-deoxyuridine incorporation demonstrate that this increase is due to the recruitment of resting memory cells into the airways. In addition, the data show that these immigrating memory cells are phenotypically distinct from the resident memory T cells of the lung airways. A similar influx of nonproliferating Sendai virus nucleoprotein 324–332/Kb-specific CD8+ memory T cells is also induced by a secondary (homologous) infection with Sendai virus. Together, these data suggest that inflammation can accelerate memory T cell migration to nonlymphoid tissues and is a part of the normal recall response during respiratory infections.

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“…The etiological agent of the disease, the singlestranded RNA influenza viruses, are responsible for an average of 114,000 hospitalizations and 20,000 deaths each year, in the United States alone (1). Influenza viruses are classified into three types (A, B, and C) of which influenza A is the most important clinically (2). The major problem in fighting influenza is the high genetic variability of the virus, resulting in the rapid emergence of variants that escape the acquired immunity induced by the available vaccines or the resistance of the pathogen to antiviral agents (1,3).…”

mentioning

confidence: 99%

Involvement of Toll-like Receptor 3 in the Immune Response of Lung Epithelial Cells to Double-stranded RNA and Influenza A Virus

Guillot

Goffic

Bloch

et al. 2005

Journal of Biological Chemistry

611

506

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Influenza A is a highly contagious single-stranded RNA virus that infects both the upper and lower respiratory tracts of humans. The host innate immune Tolllike receptor (TLR) 3 was shown previously in cells of myeloid origin to recognize the viral replicative, intermediate double-stranded RNA (dsRNA). Thus, dsRNA may be critical for the outcome of the infection. Here we first compared the activation triggered by either influenza A virus or dsRNA in pulmonary epithelial cells. We established that TLR3 is constitutively expressed in human alveolar and bronchial epithelial cells, and we describe its intracellular localization. Expression of TLR3 was positively regulated by the influenza A virus and by dsRNA but not by other inflammatory mediators, including bacterial lipopolysaccharide, the cytokines tumor necrosis factor-␣ and interleukin (IL)-1␤, and the protein kinase C activator phorbol 12-myristate 13-acetate. We also demonstrated that TLR3 contributes directly to the immune response of respiratory epithelial cells to influenza A virus and dsRNA, and we propose a molecular mechanism by which these stimuli induce epithelial cell activation. This model involves mitogen-activated protein kinases, phosphatidylinositol 3-kinase/ Akt signaling, and the TLR3-associated adaptor molecule TRIF but not MyD88-dependent activation of the transcription factors NF-B or interferon regulatory factor/interferon-sensitive response-element pathways. Ultimately, this signal transduction elicits an epithelial response that includes the secretion of the cytokines IL-8, IL-6, RANTES (regulated on activation normal T cell expressed and secreted), and interferon-␤ and the up-regulation of the major adhesion molecule ICAM-1.

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Inflammatory responses in influenza A virus infection

Cited by 237 publications

References 27 publications

Avian Influenza Virus A/HK/483/97(H5N1) NS1 Protein Induces Apoptosis in Human Airway Epithelial Cells

Avian Influenza Virus A/HK/483/97(H5N1) NS1 Protein Induces Apoptosis in Human Airway Epithelial Cells

Nonspecific Recruitment of Memory CD8+ T Cells to the Lung Airways During Respiratory Virus Infections

Involvement of Toll-like Receptor 3 in the Immune Response of Lung Epithelial Cells to Double-stranded RNA and Influenza A Virus

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