Rapid systemic uptake of allergens through the respiratory mucosa

Catholic University of Louvain, Лувен-ла-Нев, Walloon, Belgium
Journal of Allergy and Clinical Immunology (Impact Factor: 11.25). 09/2007; 120(2):472-4. DOI: 10.1016/j.jaci.2007.03.047
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    ABSTRACT: Although chronic rhinosinusitis (CRS) causes very significant morbidity, much about its pathogenesis remains uncertain. Recent studies have identified polymicrobial biofilms on the surface of sinus mucosa and Staphylococcus aureus within the sinus mucosa of patients with CRS, both with and without nasal polyps. The pathogenic implications of intramucosal bacteria in CRS are unknown. This study was designed to determine the prevalence and species of bacterial colonies within the sinus mucosa of adult patients with and without CRS and to describe the relationship of these bacterial colonies to the host immune response. Sinus mucosa from patients with and without CRS was examined using Gram and Giemsa staining, immunohistochemistry, bacterial culture, and fluorescence in situ hybridization techniques. Bacterial microcolonies were observed within the mucosa in 14 of 18 patients with CRS. In 10 of these patients colonies were positively identified as S. aureus. Staphylococcal microcolonies were observed at a lower level (1 of 8 patients) in normal sinus mucosa. There was no correlation between detection of S. aureus on the mucosal surface and microcolonization of the mucosa. Surprisingly, there was no evidence of an immune reaction to microcolonies. Indeed, fewer T lymphocytes (p = 0.03) and eosinophils (p = 0.03) were counted immediately surrounding the microcolonies compared with uninfected areas of the same tissue. Bacterial microcolonies are prevalent within paranasal sinus mucosa and are commonly S. aureus. These microcolonies do not provoke immune detection and may represent a phenotype that actively evades host immunity. This may underpin the recalcitrance of CRS to antibiotic therapy. These findings challenge classic views of both infection and mucosal immunity in human chronic disease. The presence of intramucosal bacteria in samples of normal sinus mucosa also questions the sensitivity of detecting nasal carriage of pathogens by swabbing the surface of the anterior nares.
    American Journal of Rhinology and Allergy 07/2012; 26(4):265-70. DOI:10.2500/ajra.2012.26.3779
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    ABSTRACT: Extensive data support the influence of the upper airway on lower airway inflammation and pathophysiology in allergic disease. However, few studies have focused on allergic inflammation in the nose after an isolated lower airway allergen challenge, a situation that can exist clinically when human subjects breathe primarily through the mouth, as occurs when nasally congested. This study used a mouse model to investigate whether upper airway inflammation and hyperresponsiveness were induced by an isolated lower airway allergen challenge. BALB/c mice were sensitized by systemic intraperitoneal injection of ovalbumin/saline and challenged with intratracheal ovalbumin/saline. Inflammation in the nose and lungs was assessed by cytology and histology of nasal tissues and bronchoalveolar lavage fluid (BALF), while nasal airway resistance and response were measured over 3 days post-challenge. Intratracheal application of an allergen in anaesthetized mice resulted in exclusive deposition in the lower airway. Compared to control animals, ovalbumin-sensitized mice after challenge showed bronchial hyperreactivity and increased IL-5 in the serum BALF, as well as eosinophil infiltration in the lungs. However, nasal histology of the ovalbumin-sensitized mice showed no increase in eosinophil infiltration. The nasal lavage fluid revealed no increase in eosinophils or IL-5, and the nasal airway resistance did not increase after challenge either. In a mouse allergy model, exclusive allergen challenge of the lower airway can elicit a pulmonary and systemic allergic response, but does not induce upper airway inflammatory or physiological responses.
    Allergy, asthma & immunology research 01/2015; 7(1):76-82. DOI:10.4168/aair.2015.7.1.76 · 3.08 Impact Factor
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    ABSTRACT: Airway epithelial cells are the first to encounter aeroallergens and therefore have recently become an interesting target of many studies investigating their involvement in the modulation of allergic inflammatory responses. Disruption of a passive structural barrier composed of epithelial cells by intrinsic proteolytic activity of allergens may facilitate allergen penetration into local tissues and additionally affect chronic and ongoing inflammatory processes in respiratory tissues. Furthermore, the ability of rhinoviruses to disrupt and interfere with epithelial tight junctions may alter the barrier integrity and enable a passive passage of inhaled allergens through the airway epithelium. On the other hand, epithelial cells are no longer considered to act only as a physical barrier toward inhaled allergens, but also to actively contribute to airway inflammation by detecting and responding to environmental factors. Epithelial cells can produce mediators, which may affect the recruitment and activation of more specialized immune cells to the local tissue and also create a microenvironment in which these activated immune cells may function and propagate the inflammatory processes. This review presents the dual role of epithelium acting as a passive and active barrier when encountering an inhaled allergen and how this double role contributes to the start of local immune responses.
    Allergy 12/2012; 68(2). DOI:10.1111/all.12080 · 6.00 Impact Factor