Type I Interferon Potentiates IgA Immunity to Respiratory Syncytial Virus Infection During Infancy

Diego R Hijano,Sridhar Jaligama,David Finkelstein,Stephania A Cormier,Heather Tillman,David T Siefker,Luan D Vu,Bishwas Shrestha,Jordy Saravia,Dahui You

doi:10.1038/s41598-018-29456-w

Abstract

Respiratory syncytial virus (RSV) infection is the most frequent cause of hospitalization in infants and young children worldwide. Although mucosal RSV vaccines can reduce RSV disease burden, little is known about mucosal immune response capabilities in children. Neonatal or adult mice were infected with RSV; a subset of neonatal mice received interferon alpha (IFN-α) (intranasal) prior to RSV infection. B cells, B cell activating factor (BAFF) and IgA were measured by flow cytometry. RSV specific IgA was measured in nasal washes. Nasal associated lymphoid tissue (NALT) and lungs were stained for BAFF and IgA. Herein, we show in a mouse model of RSV infection that IFN-α plays a dual role as an antiviral and immune modulator and age-related differences in IgA production upon RSV infection can be overcome by IFN-α administration. IFN-α administration before RSV infection in neonatal mice increased RSV-specific IgA production in the nasal mucosa and induced expression of the B-cell activating factor BAFF in NALT. These findings are important, as mucosal antibodies at the infection site, and not serum antibodies, have been shown to protect human adults from experimental RSV infection.

Highlights

There are well-defined differences between innate and adaptive immune responses of infants and adults[11,12]
Respiratory syncytial virus (RSV) viral load in Nasal associated lymphoid tissue (NALT) was significantly lower in neonatal mice receiving IFN-α prior to RSV infection than in neonatal mice not receiving IFN-α or adult mice infected with RSV (Fig. 1b)
We describe a dual role for IFN-α as an antiviral and immune modulator that goes beyond primary RSV infection

Summary

Introduction

There are well-defined differences between innate and adaptive immune responses of infants and adults[11,12]. Neonatal mouse models of RSV infection have revealed the key role of age-dependent differences in RSV pathogenesis[13,14,15,16], of which those related to type I interferon (IFN) production are of special interest. We use adult and neonatal mice infected with RSV to reveal the critical role of IgA at the nasal mucosa and an age-dependent deficit in IgA production. We show that this deficit in neonatal mice is due to decreased B-cell activation and can be ameliorated by IFN-α supplementation to the nasal mucosa before RSV infection

Methods

Results

Conclusion