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Review
. 2015 Oct;136(4):838-47.
doi: 10.1016/j.jaci.2015.06.034. Epub 2015 Aug 12.

Neutrophils in respiratory syncytial virus infection: A target for asthma prevention

Ruben J Geerdink  1 , Janesh Pillay  2 , Linde Meyaard  1 , Louis Bont  3
Affiliations
Review

Neutrophils in respiratory syncytial virus infection: A target for asthma prevention

Ruben J Geerdink et al. J Allergy Clin Immunol. 2015 Oct.

Abstract

Lower respiratory tract infections by respiratory syncytial virus (RSV) are the foremost cause of infant hospitalization and are implicated in lasting pulmonary impairment and the development of asthma. Neutrophils infiltrate the airways of pediatric patients with RSV-induced bronchiolitis in vast numbers: approximately 80% of infiltrated cells are neutrophils. However, why neutrophils are recruited to the site of viral respiratory tract infection is not clear. In this review we discuss the beneficial and pathologic contributions of neutrophils to the immune response against RSV infection. Neutrophils can limit viral replication and spread, as well as stimulate an effective antiviral adaptive immune response. However, low specificity of neutrophil antimicrobial armaments allows for collateral tissue damage. Neutrophil-induced injury to the airways during the delicate period of infant lung development has lasting adverse consequences for pulmonary architecture and might promote the onset of asthma in susceptible subjects. We suggest that pharmacologic modulation of neutrophils should be explored as a viable future therapy for severe RSV-induced bronchiolitis and thereby prevent the inception of subsequent asthma. The antiviral functions of neutrophils suggest that targeting of neutrophils in patients with RSV-induced bronchiolitis is best performed under the umbrella of antiviral treatment.

Keywords: Neutrophil; asthma; asthma prevention; immune regulation; immunopathology; lower respiratory tract infection; neutrophil extracellular traps; respiratory syncytial virus; respiratory syncytial virus bronchiolitis; treatment.

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Figures

Fig 1
Fig 1
Schematic representation of the tentative relationship between neutrophil-induced lung damage and airway sensitization during RSV-induced bronchiolitis and subsequent susceptibility to asthma.
Fig 2
Fig 2
Protective and lung-injurious roles of neutrophils during respiratory tract viral infection. Neutrophil-induced mucus production limits access of viral particles to the epithelium but obstructs airflow. Degranulation releases antimicrobial mediators that are also cytotoxic to host cells. Phagocytosis of (opsonized) viral particles and virus-infected cells limits viral spread. NETs capture and deactivate viral particles but also damage healthy bystander cells. ECM, Extracellular matrix; PRMs, pattern recognition molecules.
Fig 3
Fig 3
Neutrophils regulate immune responses. A and B, Neutrophils directly and indirectly present viral antigen to elicit CD8+ T-cell responses. C, In collaboration with DCs, neutrophils maintain NK cell homeostasis. D, Neutrophils recruit, activate, and polarize DCs but can also suppress DC activity. E, Splenic neutrophils produce cytokines to induce immunoglobulin class-switch recombination, somatic hypermutation, and antibody production in marginal zone B cells. F, T-cell activity can be suppressed by neutrophils through direct interactions with T cells and by limiting stimulatory interactions between T cells and DCs. APC, Antigen-presenting cell; APRIL, a proliferation-inducing ligand; BAFF, B cell–activating factor of the TNF family; CEACAM1, carcinoembryonic antigen-related cell adhesion molecule 1; DC-SIGN, dendritic cell–specific intercellular adhesion molecule 3–grabbing nonintegrin; MZ, marginal zone; TCR, T-cell receptor.
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