Induction of Apoptosis and Subsequent Phagocytosis of Virus-Infected Cells As an Antiviral Mechanism.

Firzan Nainu,Yoshinobu Nakanishi,Akiko Shiratsuchi

doi:10.3389/fimmu.2017.01220

Firzan Nainu, Yoshinobu Nakanishi + Show 1 more

Open Access

https://doi.org/10.3389/fimmu.2017.01220

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Abstract

Viruses are infectious entities that hijack host replication machineries to produce their progeny, resulting, in most cases, in disease and, sometimes, in death in infected host organisms. Hosts are equipped with an array of defense mechanisms that span from innate to adaptive as well as from humoral to cellular immune responses. We previously demonstrated that mouse cells underwent apoptosis in response to influenza virus infection. These apoptotic, virus-infected cells were then targeted for engulfment by macrophages and neutrophils. We more recently reported similar findings in the fruit fly Drosophila melanogaster, which lacks adaptive immunity, after an infection with Drosophila C virus. In these experiments, the inhibition of phagocytosis led to severe influenza pathologies in mice and early death in Drosophila. Therefore, the induction of apoptosis and subsequent phagocytosis of virus-infected cells appear to be an antiviral innate immune mechanism that is conserved among multicellular organisms. We herein discuss the underlying mechanisms and significance of the apoptosis-dependent phagocytosis of virus-infected cells. Investigations on the molecular and cellular features responsible for this underrepresented virus–host interaction may provide a promising avenue for the discovery of novel substances that are targeted in medical treatments against virus-induced intractable diseases.

Highlights

Viruses are one of the most abundant entities present in the environment
In order to examine the role of apoptosis, we investigated whether influenza virus-infected cells are targeted for engulfment by phagocytes
Phagocytosis was decreased further after the simultaneous RNA interference (RNAi) of both receptors. These findings collectively suggested that Drosophila C virus (DCV)-infected cells are subjected to apoptosis-dependent phagocytosis by Drosophila phagocytes, depending on, at least partly, the eat-me signal PS and engulfment receptors Draper and integrin αPS3–βν

Summary

Introduction

Viruses are one of the most abundant entities present in the environment. All species, including microbial pathogens, such as bacteria and fungi, are subject to infections by viruses [1, 2]. The ligands for engulfment receptors are called eat-me signals or markers for phagocytosis, which appear on the cell surface during the apoptotic process [37, 39, 40]. Previous studies demonstrated that HeLa cells and Madin–Darby canine kidney cells become apoptotic upon influenza A virus infection, characterized by the cleavage of host chromosomal DNA [48], condensation of chromatin [48], surface exposure of PS [49], and activation of initiator and effector caspases [50].

Results

Conclusion