Respiratory epithelial cells in innate immunity to influenza virus infection

Sanders, Catherine J.; Doherty, Peter C.; Thomas, Paul G.

doi:10.1007/s00441-010-1043-z

Cited by 158 publications

(161 citation statements)

References 86 publications

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“…A variety of host cells, including ciliated epithelial cells, type I and II alveolar cells, and immune cells, are infected by IAV within the respiratory tract (1)(2)(3)(4). IAV-infected cells are eliminated through two major mechanisms: viral replication-mediated apoptosis or necrosis (5,6) and immune system-mediated viral clearance (7,8). The pathogenesis and outcome of influenza viral infection are the result of the balance between host defense mechanisms and viral pathogenicity.…”

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confidence: 99%

Swift and Strong NK Cell Responses Protect 129 Mice against High-Dose Influenza Virus Infection

Zhou

Wang

et al. 2016

The Journal of Immunology

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It is generally unclear what roles NK cells play during influenza virus infection with regard to different host genetic backgrounds. In this study, we show that in six inbred mouse strains, NK cells play an important protective role only in 129 mice during high-dose influenza A H1N1 virus infection. Swift and strong NK cell responses efficiently control early pulmonary viral replication in 129 mice, providing survival privilege. In addition, we identified that early activation of TLRs and RIG-I signaling in 129 mice resulted in quick production of type 1 IFNs and inflammatory cytokines, which are important reasons for the swift kinetics of NK cell responses post influenza virus infection. Thus, under different microenvironments, NK cells play differential roles against viral infections. The kinetics and magnitude of NK cell responses correlate with the distinct roles that NK cells play against influenza virus infections. Thus, our works further our understandings about the complex role of NK cells during influenza virus infection.

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confidence: 99%

Swift and Strong NK Cell Responses Protect 129 Mice against High-Dose Influenza Virus Infection

Zhou

Wang

et al. 2016

The Journal of Immunology

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“…Following infection, viral nucleic acids bind to pattern recognition receptors (PRR) within epithelial and immune cells (32) causing high levels of inflammatory cytokines, including TNF-a, IL-6, IL-1a/b, IFN a/b, CXCL9/10, MIP-1a/b, and MCP-1 (27), to be secreted in the lung. The presence of these cytokines, and others, alters the lung microenvironment and initiates the trafficking of immune cells such as macrophages, dendritic cells, and neutrophils to the site of infection.…”

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confidence: 99%

Early Cytokine Dysregulation and Viral Replication Are Associated with Mortality During Lethal Influenza Infection

et al. 2014

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Infection with influenza A virus (IAV) leads to acute lung injury and possibly fatal complications, especially in immunocompromised, elderly, or chronically infected individuals. Therefore, it is important to study the factors that lead to pathology and mortality in infected hosts. In this report, we analyze immune responses to infection at a sublethal (0.1 LD 50 ) and lethal (1 LD 50 ) dose of the highly pathogenic IAV A/Puerto Rico/8/34 (PR8). Our experiments revealed that infection with a 1 LD 50 dose induced peak viral titers at day 2 compared to day 4 in the 0.1 LD 50 dose. Moreover, early cytokine dysregulation was observed in the lethal dose with significantly elevated levels of IFN-a, TNF-a, CXCL9, IL-6, and MCP-1 produced at day 2. Early inflammatory responses following infection with 1 LD 50 correlated with a greater influx of neutrophils into the lung. However, depletion of neutrophils enhanced morbidity following IAV infection. Though no differences in CD8 + cell function were observed, CD4 + effector responses were impaired in the lungs 8 days after infection with 1 LD 50 . Histological analysis revealed significant pathology in lethally infected mice at day 2 and day 6 postinfection, when viral titers remained high. Treating lethally infected mice with oseltamivir inhibited viral titers to sublethal levels, and abrogated the pathology associated with the lethal dose. Together, these results suggest that early cytokine dysregulation and viral replication play a role in pulmonary damage and high mortality in lethally infected mice.

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“…These findings allowed us to utilize HPAEpiCs to examine the role of RLR signaling in AECs in this present study. Human AECs can be divided into two populations: ATI and ATII epithelial cells [23]. ATI cells reside in the alveoli of the lung where they are separated from inspired air from the blood in the capillaries [24].…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have shown that ATII cells are involved in inflammatory responses, including antiviral innate immune responses [23]. HPAEpiCs have been reported to contain > 96% ATII cells [25] and are known to respond to foreign RNA stimuli (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

Retinoic acid-inducible gene-I-like receptor (RLR)-mediated antiviral innate immune responses in the lower respiratory tract: Roles of TRAF3 and TRAF5

Chiba

Matsumiya

Satoh

et al. 2015

Biochemical and Biophysical Research Communications

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Upon viral infection, the cytoplasmic viral sensor retinoic acid-inducible gene-I (RIG-I) recognizes viral RNA to activate antiviral signaling to induce type I interferon (IFN).RIG-I-like receptors (RLRs) activate antiviral signaling in a tissue-specific manner. The molecular mechanism underlying antiviral signaling in the respiratory system remains unclear.We studied antiviral signaling in the lower respiratory tract (LRT), which is the site of many harmful viral infections. Epithelial cells of the LRT can be roughly divided into two groups: bronchial epithelial cells (BECs) and pulmonary alveolar epithelial cells (AECs). These two cell types exhibit different phenotypes; therefore, we hypothesized that these cells may play different roles in antiviral innate immunity. We found that BECs exhibited higher antiviral activity than AECs. TNF receptor-associated factor 3 (TRAF3) has been shown to be a crucial molecule in RLR signaling. The expression levels of TRAF3 and TRAF5, which have conserved domains that are nearly identical, in the LRT were examined. We found that the bronchus exhibited the highest expression levels of TRAF3 and TRAF5 in the LRT. These findings suggest the importance of the bronchus in antiviral innate immunity in the LRT and indicate that TRAF3 and TRAF5 may contribute to RLR signaling.

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Respiratory epithelial cells in innate immunity to influenza virus infection

Cited by 158 publications

References 86 publications

Swift and Strong NK Cell Responses Protect 129 Mice against High-Dose Influenza Virus Infection

Swift and Strong NK Cell Responses Protect 129 Mice against High-Dose Influenza Virus Infection

Early Cytokine Dysregulation and Viral Replication Are Associated with Mortality During Lethal Influenza Infection

Retinoic acid-inducible gene-I-like receptor (RLR)-mediated antiviral innate immune responses in the lower respiratory tract: Roles of TRAF3 and TRAF5

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