Herpes Simplex Virus Type 1 Infection Facilitates Invasion of Staphylococcus aureus into the Nasal Mucosa and Nasal Polyp Tissue

Xiangdong Wang,Mario Vaneechoutte,Sarah Glorieux,Olga Krysko,Nan Zhang,Claus Bachert,Gabriele Holtappels,Luo Zhang,Hans J Nauwynck,Demin Han,Michael Otto

doi:10.1371/journal.pone.0039875

Xiangdong Wang, Mario Vaneechoutte + Show 9 more

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https://doi.org/10.1371/journal.pone.0039875

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Abstract

Background Staphylococcus aureus (S. aureus) plays an important role in the pathogenesis of severe chronic airway disease, such as nasal polyps. However the mechanisms underlying the initiation of damage and/or invasion of the nasal mucosa by S. aureus are not clearly understood. The aim of this study was to investigate the interaction between S. aureus and herpes simplex virus type 1 (HSV1) in the invasion of the nasal mucosa and nasal polyp tissue.Methodology/Principal FindingsInferior turbinate and nasal polyp samples were cultured and infected with either HSV1 alone, S. aureus alone or a combination of both. Both in turbinate mucosa and nasal polyp tissue, HSV1, with or without S. aureus incubation, led to focal infection of outer epithelial cells within 48 h, and loss or damage of the epithelium and invasion of HSV1 into the lamina propria within 72 h. After pre-infection with HSV1 for 24 h or 48 h, S. aureus was able to pass the basement membrane and invade the mucosa. Epithelial damage scores were significantly higher for HSV1 and S. aureus co-infected explants compared with control explants or S. aureus only-infected explants, and significantly correlated with HSV1-invasion scores. The epithelial damage scores of nasal polyp tissues were significantly higher than those of inferior turbinate tissues upon HSV1 infection. Consequently, invasion scores of HSV1 of nasal polyp tissues were significantly higher than those of inferior turbinate mucosa in the HSV1 and co-infection groups, and invasion scores of S. aureus of nasal polyp tissues were significantly higher than those of inferior turbinate tissues in the co-infection group.Conclusions/SignificanceHSV1 may lead to a significant damage of the nasal epithelium and consequently may facilitate invasion of S. aureus into the nasal mucosa. Nasal polyp tissue is more susceptible to the invasion of HSV1 and epithelial damage by HSV1 compared with inferior turbinate mucosa.

Highlights

Staphylococcus aureus, a gram-positive bacterium commonly found as part of the normal microflora of the human skin, the upper respiratory tract and the intestinal tract, has been shown to cause a number of illnesses ranging from minor skin infections to life-threatening diseases such as pneumonia, meningitis, toxic shock, osteomyelitis, endocarditis, bacteremia, and autoimmune disorders.1 The mechanisms underlying S. aureus pathogenicity involve a variety of staphylococcal enterotoxins (SAEs) that act as superantigens [1,2], capable of activating T cells and B cells
As bacterial infection has been demonstrated often to be secondary to viral infection [8], it is tempting to speculate that an interaction between viral and S. aureus infections is likely, at least in part, to be responsible for the invasion of S. aureus into the nasal mucosa of these patients
Our study demonstrated that prior infection of human nasal explants with herpes simplex virus type 1 (HSV1) in the absence or presence of subsequent S. aureus-infection led to focal infection of epithelial cells after mock/S.aureus-treatment following 24 h of preinfection with HSV1 and loss or damage of the epithelium accompanied by invasion of HSV1 into the lamina propria following 48 h of pre-infection with HSV1

Summary

Introduction

Staphylococcus aureus, a gram-positive bacterium commonly found as part of the normal microflora of the human skin, the upper respiratory tract ( the nares) and the intestinal tract, has been shown to cause a number of illnesses ranging from minor skin infections to life-threatening diseases such as pneumonia, meningitis, toxic shock, osteomyelitis, endocarditis, bacteremia, and autoimmune disorders. The mechanisms underlying S. aureus pathogenicity involve a variety of staphylococcal enterotoxins (SAEs) that act as superantigens [1,2], capable of activating T cells and B cells. Several studies have indicated that SAEs play an important role in the pathogenesis of upper airways disease, chronic rhinosinusitis and nasal polyposis [3,4,5,6,7], with more recent findings suggesting that SAEs may be involved in the pathogenesis of asthma [8,9,10]. Despite evidence for the high colonisation rates of the airway mucosa by S. aureus [7],7 the mechanisms underlying the damage or invasion of the nasal mucosa by S. aureus are not clearly understood. Staphylococcus aureus (S. aureus) plays an important role in the pathogenesis of severe chronic airway disease, such as nasal polyps. The mechanisms underlying the initiation of damage and/or invasion of the nasal mucosa by S. aureus are not clearly understood. The aim of this study was to investigate the interaction between S. aureus and herpes simplex virus type 1 (HSV1) in the invasion of the nasal mucosa and nasal polyp tissue

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