Dataset Information

High Expression of IL-36? in Influenza Patients Regulates Interferon Signaling Pathway and Causes Programmed Cell Death During Influenza Virus Infection.

ABSTRACT: As a severe complication of influenza infection, acute respiratory distress syndrome (ARDS) has higher morbidity and mortality. Although IL-36? has been proven to promote inflammation at epithelial sites and protect against specific pathogen infection, the detailed roles in severe influenza infection remain poorly understood. In this study, we have found that the expression of IL-36? is higher in influenza-induced ARDS patients than healthy individuals. IL-36? was induced in human lung epithelial cells and peripheral blood mononuclear cells by Influenza A virus (IAV) infection, and its induction was synergistically correlated with initiation of the cyclooxygenase-2 (COX-2)/Prostaglandin E2 (PGE2) axis. We also have found that expression of superficial IL-36R was elevated in severe influenza patients and in IAV-stimulated cells. Furthermore, although IL-36? enhanced the induction of type I and III interferons (IFNs), which promoted IAV-mediated IFN-stimulated STAT1 and STAT2 phosphorylated inhibition in lung epithelial cells, the downstream interferon-stimulated genes (ISGs) were not affected. Finally, we have revealed that IL-36? treatment could promote apoptosis and inhibit autophagy in the early stages of IAV infection. Overall, these findings demonstrated IL-36? is a critical host immune factor in response to IAV infection. It has potential activity in the regulation of the interferon signaling pathway and was involved in different types of programmed cell death in human airway epithelial cells as well.

SUBMITTER: Liu S

PROVIDER: S-EPMC7642405 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

High Expression of IL-36γ in Influenza Patients Regulates Interferon Signaling Pathway and Causes Programmed Cell Death During Influenza Virus Infection.

Liu Shuai S Li Hui H Wang Yeming Y Li Haibo H Du Sisi S Zou Xiaohui X Zhang Xulong X Cao Bin B

Frontiers in immunology 20201022

As a severe complication of influenza infection, acute respiratory distress syndrome (ARDS) has higher morbidity and mortality. Although IL-36γ has been proven to promote inflammation at epithelial sites and protect against specific pathogen infection, the detailed roles in severe influenza infection remain poorly understood. In this study, we have found that the expression of IL-36γ is higher in influenza-induced ARDS patients than healthy individuals. IL-36γ was induced in human lung epithelia ...[more]

PMID: 33193319

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Project description:A major pathophysiologic mechanism in sepsis is impaired host immunity which results in failure to eradicate invading pathogens and increased susceptibility to secondary infections. Although many immunosuppressive mechanisms exist, increased expression of the inhibitory receptor programmed cell death 1 (PD-1) and its ligand (PD-L1) are thought to play key roles. The newly recognized phenomenon of T cell exhaustion is mediated in part by PD-1 effects on T cells. This study tested the ability of anti-PD-1 and anti-PD-L1 antibodies to prevent apoptosis and improve lymphocyte function in septic patients.Blood was obtained from 43 septic and 15 non-septic critically-ill patients. Effects of anti-PD-1, anti-PD-L1, or isotype-control antibody on lymphocyte apoptosis and interferon gamma (IFN-?) and interleukin-2 (IL-2) production were quantitated by flow cytometry.Lymphocytes from septic patients produced decreased IFN-? and IL-2 and had increased CD8 T cell expression of PD-1 and decreased PD-L1 expression compared to non-septic patients (P<0.05). Monocytes from septic patients had increased PD-L1 and decreased HLA-DR expression compared to non-septic patients (P<0.01). CD8 T cell expression of PD-1 increased over time in ICU as PD-L1, IFN-?, and IL2 decreased. In addition, donors with the highest CD8 PD-1 expression together with the lowest CD8 PD-L1 expression also had lower levels of HLA-DR expression in monocytes, and an increased rate of secondary infections, suggestive of a more immune exhausted phenotype. Treatment of cells from septic patients with anti-PD-1 or anti-PD-L1 antibody decreased apoptosis and increased IFN-? and IL-2 production in septic patients; (P<0.01). The percentage of CD4 T cells that were PD-1 positive correlated with the degree of cellular apoptosis (P<0.01).In vitro blockade of the PD-1:PD-L1 pathway decreases apoptosis and improves immune cell function in septic patients. The current results together with multiple positive studies of anti-PD-1 and anti-PD-L1 in animal models of bacterial and fungal infections and the relative safety profile of anti-PD-1/anti-PD-L1 in human oncology trials to date strongly support the initiation of clinical trials testing these antibodies in sepsis, a disorder with a high mortality.

Dataset Information

High Expression of IL-36? in Influenza Patients Regulates Interferon Signaling Pathway and Causes Programmed Cell Death During Influenza Virus Infection.

Publications

High Expression of IL-36γ in Influenza Patients Regulates Interferon Signaling Pathway and Causes Programmed Cell Death During Influenza Virus Infection.

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