Reactive Oxygen Species Induce Antiviral Innate Immune Response through IFN-λ Regulation in Human Nasal Epithelial Cells

Abstract

This study sought to explore the role of the IFN-related innate immune responses (IFN-b and IFN-l) and of reactive oxygen species (ROS) after influenza A virus (IAV) infection for antiviral innate immune activity in normal human nasal epithelial (NHNE) cells that are highly exposed to IAV. Passage-2 NHNE cells were inoculated with the IAV WSN/33 for 1, 2, and 3 days to assess the capacity of IFN and the relationship between ROS generation and IFN-l secretion for controlling IAV infection. Viral titers and IAV mRNA levels increased after infection. In concert with viral titers, we found that the generation of IFNs, such as IFN-b, IFN-l1, and IFN-l2/3, was induced after IAV infection until 3 days after infection. The induction of IFN-l gene expression and protein secretion may be predominant after IAV infection. Similarly, we observed that intracellular ROS generation increased 60 minutes after IAV infection. Viral titers and mRNA levels of IAV were significantly higher in cases with scavenging ROS, in cases with an induced IFN-l mRNA level, or where the secreted protein concentration of IFN-l was attenuated after the suppression of ROS generation. Both mitochondrial and dual oxidase (Doux)2-generated ROS were correlated with IAV mRNA and viral titers. The inhibition of mitochondrial ROS generation and the knockdown of Duox2 gene expression highly increased IAV viral titers and decreased IFN-l secretion. Our findings suggest that the production of ROS may be responsible for IFN-l secretion to control IAV infection. Both mitochondria and Duox2 are possible sources of ROS generation, which is required to initiate an innate immune response in NHNE cells.

Oxidative Stress during HIV Infection: Mechanisms and Consequences

“…Mitochondrial dysfunction is a general mechanism of ROS production common for most viral infections [111–113]. NADPH oxidases and CYP2E1 serve as the major sources of ROS in infections with human hepatitis C, influenza, and respiratory syncytial viruses [114–121].…”

The Induction of Pattern-Recognition Receptor Expression against Influenza A Virus through Duox2-Derived Reactive Oxygen Species in Nasal Mucosa

“…Furthermore, interesting lines of research describe Duox-mediated ROS generation as an integral part of the host defense system at mucosal surfaces (10,12,13). Recently, it has been verified that Duox2 is primarily responsible for protection against viral invaders and plays an important role in antiviral innate immunity (14). However, the distinct relationship between Duox2derived ROS and IFN-related innate immune responses is not fully understood.…”

Antimicrobial Organometallic Dendrimers with Tunable Activity against Multidrug-Resistant Bacteria

“…23 The presence of ROS induces oxidative stress, a cellular defence strategy employed against a broad spectrum of microbes. [50][51][52][53] Indeed, a number of redox-active organometallic 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 25 compounds enhance antimicrobial activity via the induction of cellular oxidative stress. 23 Using the dichlorodihydrofluorescein (H 2 DCF) oxidative assay, 30,54 we probed the induction of cellular oxidative stress by DEN1-DEN3 on MRSA.…”