Neutrophil in viral infections, friend or foe?

doi:10.1016/j.virusres.2012.11.002

Virus Research

Volume 171, Issue 1, January 2013, Pages 1-7

https://doi.org/10.1016/j.virusres.2012.11.002 Get rights and content

Abstract

Polymorphonuclear leukocytes or neutrophils are the first immune cells to the site of injury and microbial infection. Neutrophils are crucial players in controlling bacterial and fungal infections, and in particular secondary infections, by phagocytosis, degranulation and neutrophil extracellular traps (NETs). While neutrophils have been shown to play important roles in viral pathogenesis, there is a lack of detailed investigation. In this article, we will review recent progresses toward understanding the role of neutrophils in viral pathogenesis.

Section snippets

Background

Neutrophils comprise the largest number of immune cells in the human body, approximately 80% at any given time, mainly during infections (Bai et al., 2010, Le Goffic et al., 2011, McNamara et al., 2003). While the majority of these cells remain housed in the bone marrow or immune centers (e.g. spleen and lymph nodes), about 2% of the total neutrophil population circulates in the blood (Navarini et al., 2009). These are short-lived cells, usually for 6–20 h in circulation under healthy conditions

Protective roles

Neutrophils comprise a major element of the innate immune system and demolish invading microbes primarily by phagocytosing bacteria, fungi and virions (Choi and Dumler, 2003, Chtanova et al., 2008, Crameri and Blaser, 2002, Ferrante, 1989, Hachicha et al., 1998, Nathan, 2006, Soehnlein, 2009a, Tate et al., 2009, Wang et al., 2008). Viral infections will usually weaken and impair the host's immune system opening the way for opportunistic pathogens, such as bacteria or fungi, to take advantage of

Double-edged sword role

Neutrophils must be tightly regulated otherwise tissue damage is inevitable due to increased infiltration of these cells, which may lead to vascular leakage and high release of catalytic proteins and NETs. During the resolution phase of immune responses, clearance of neutrophils and other recruited immune cells occurs. Any defects in this process will cause inflammatory diseases (Croker et al., 2012) or susceptibility to secondary infections. Too many NETs and high amounts of microbial material

Neutrophils as viral transport vessels

Neutrophils are the most abundant cells circulating in the human blood stream. Interestingly, neutrophils have shown to be productively infected by West Nile virus (WNV), implying that neutrophils may be responsible for WNV dissemination in the peripheral and central nervous system (CNS). Higher titers of WNV were detected in neutrophils compared to macrophages supporting the notion of viral replication in neutrophils (Bai et al., 2010) (Fig. 2a). In addition, both positive- and negative-sense

Concluding remarks

Neutrophils, as a major component in the mammalian innate immune system, have essential roles in the battle with invading bacteria, fungi as well as viruses. More and more attentions have been drawn to dissecting the roles of neutrophils in viral pathogenesis; however, we still know very little about the true nature of neutrophils during the course of viral infections. Neutrophils appear to contribute to controlling viral infections, but unbalanced recruitment may cause severe damage to the

Acknowledgements

This work was supported in part by the Mississippi INBRE funded by grants from the National Center for Research Resources (5P20RR016476-11) and the National Institute of General Medical Sciences (8 P20 GM103476-11) from the National Institutes of Health.

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Citation Excerpt :
Thus, we conclude that proteinase 3, cathepsin G, and elastase show virucidal effects against hRSV. Drescher and Bai (2012) [25] and Agraz-Cibrian et al. (2017) [26] reviewed the role of NETs in viral infections. NET release occurs in the presence of different viruses, and NETs exhibit antiviral activity against many of the viruses studied.
Human respiratory syncytial virus (hRSV) is an infectious agent in infants and young children which there are no vaccines or drugs for treatment. Neutrophils are recruited for airway, where they are stimulated by hRSV to release large amounts of neutrophil extracellular traps (NETs). NETs are compound by DNA and proteins, including microbicidal enzymes. They constitute a large part of the mucus accumulated in the lung of patients, compromising their breathing capacity. In contrast, NETs can capture/inactivate hRSV, but the molecules responsible for this effect are unknown.
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Through in vitro assays using HEp-2 cells, we observed that elastase, proteinase-3, and cathepsin-G, but not myeloperoxidase, showed virucidal effects even at non-cytotoxic concentrations. Elastase and proteinase-3, but not cathepsin-G, cleaved viral F-protein, which is responsible for viral adhesion and fusion with the target cells. Molecular docking analysis indicated the interaction of these macromolecules in the antigenic regions of F-protein through the active regions of the enzymes.
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ReviewNeutrophil in viral infections, friend or foe?

Abstract

Section snippets

Background

Protective roles

Double-edged sword role

Neutrophils as viral transport vessels

Concluding remarks

Acknowledgements

Cytokines and fungal infections

British Journal of Haematology

A paradoxical role for neutrophils in the pathogenesis of West Nile virus

Journal of Infectious Diseases

IL-10 signaling blockade controls murine West Nile virus infection

PLoS Pathogens

New concepts of the pathogenesis of cystic fibrosis lung disease

European Respiratory Journal

Dynamics of immune cell recruitment during West Nile encephalitis and identificaiton of a new CD19+ B220-BST-2+ leukocyte population

Journal of Immunology

Neutrophil extracellular traps kill bacteria

Science

Beneficial suicide: why neutrophils die to make NETs

Nature Reviews Microbiology

Neutrophil extracellular traps: is immunity the second function of chromatin?

Journal of Cell Biology

Early induction and late abrogation of respiratory burst in A. phagocytophilum-infected neutrophils

Annals of the New York Academy of Sciences

Dynamics of neutrophil migration in lymph nodes during infection

Immunity

Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood

Nature Medicine

Influenza A virus accelerates neutrophil apoptosis and markedly potentiates apoptotic effects of bacteria

Blood

Modulation of granulocyte survival and programmed cell death by cytokines and bacterial products

Blood

Allergy and immunity to fungal infections and colonization

European Respiratory Journal

Towards a four-dimensional view of neutrophils

Cell-specific IRF-3 responses protect against West Nile virus infection by interferon-depenednt and -independent mechanisms

PLoS Pathogens

Herpetic eye disease: immunopathogenesis and therapeutic measures

Expert Reviews in Molecular Medicine

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Journal of Immunology

The leukocyte response during viral respiratory illness in man

Annals of Internal Medicine

Neutrophil apoptosis during viral infections

Open Virology Journal

Role of the respiratory burst in co-operative reduction in neutrophil survival by influenza A virus and Escherichia coli

Journal of Medical Microbiology

An oligodeoxynucleotide capable of lessening acute lung inflammatory injury in mice infected by influenza virus

Biochemical and Biophysical Research Communications

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Infection and Immunity

IL-17, produced by lymphocytes and neutrophils, is necessary for lipopolysaccharide-induced airway neutrophilia: IL-15 as a possible trigger

Journal of Immunology

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Journal of Cell Biology

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European Journal of Pharmacology

Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus

Science Translational Medicine

Comparison of interferon-gamma, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor for priming leukocyte-mediated hyphal damage of opportunistic fungal pathogens

Journal of Infectious Diseases

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PLoS Pathogens

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Clinical and Experimental Immunology

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PLoS Neglected Tropical Diseases

Survival of Staphylococcus aureus inside neutrophils contributes to infection

Journal of Immunology

Cytomegalovirus-infected endothelial cells recruit neutrophils by the secretion of C-X-C chemokines and transmit virus by direct neutrophil–endothelial cell contact and during neutrophils transendothelial migration

Journal of Infectious Diseases

H5N1 infection of the respiratory tract and beyond: a molecular pathology study

Lancet

ETosis: a microbicidal mechanism beyond cell death

Journal of Parasitology Research

Regulation of chemokine gene expression in human peripheral blood neutrophils phagocytosing microbial pathogens

Journal of Immunology

Review
Neutrophil in viral infections, friend or foe?