The Multifunctional Host Defense Peptide SPLUNC1 Is Critical for Homeostasis of the Mammalian Upper Airway

Glen Mcgillivary,Lauren O Bakaletz,Frank R Deleo

doi:10.1371/journal.pone.0013224

Glen Mcgillivary, Lauren O Bakaletz + Show 1 more

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https://doi.org/10.1371/journal.pone.0013224

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Abstract

Otitis media (OM) is a highly prevalent pediatric disease caused by normal flora of the nasopharynx that ascend the Eustachian tube and enter the middle ear. As OM is a disease of opportunity, it is critical to gain an increased understanding of immune system components that are operational in the upper airway and aid in prevention of this disease. SPLUNC1 is an antimicrobial host defense peptide that is hypothesized to contribute to the health of the airway both through bactericidal and non-bactericidal mechanisms. We used small interfering RNA (siRNA) technology to knock down expression of the chinchilla ortholog of human SPLUNC1 (cSPLUNC1) to begin to determine the role that this protein played in prevention of OM. We showed that knock down of cSPLUNC1 expression did not impact survival of nontypeable Haemophilus influenzae, a predominant causative agent of OM, in the chinchilla middle ear under the conditions tested. In contrast, expression of cSPLUNC1 was essential for maintenance of middle ear pressure and efficient mucociliary clearance, key defense mechanisms of the tubotympanum. Collectively, our data have provided the first in vivo evidence that cSPLUNC1 functions to maintain homeostasis of the upper airway and, thereby, is critical for protection of the middle ear.

Highlights

Otitis media (OM), or inflammation of the middle ear, is the second most common pediatric infectious disease
SPLUNC1 is an antimicrobial host defense family of proteins (APs) that is abundantly expressed in the upper airway [28], the role that this protein might play in prevention of OM is not completely understood
We utilized a small interfering RNA (siRNA)-based approach to knock down expression of the chinchilla homologue of human SPLUNC1 and thereby demonstrated that this AP was critical for homeostasis of the tubotympanum

Summary

Introduction

Otitis media (OM), or inflammation of the middle ear, is the second most common pediatric infectious disease. Over 80% of children develop a least one incident of OM by three years of age and more than half of children experience multiple episodes of this disease [1,2]. The estimated cost per episode of OM in the US is in the hundreds of dollars and more than 15 million antibiotic prescriptions are written each year for the treatment of OM. When host airway defenses are compromised, most typically by upper respiratory tract (URT) viruses, these bacteria can behave as opportunistic pathogens and ascend the Eustachian tube (ET) to gain access to the middle ear [9,10,11]. It is important to understand and characterize host defense mechanisms that contribute to prevention of OM and promote overall health of the uppermost respiratory tract

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