Chronic Exposure to Innocuous Antigen in Sensitized Mice Leads to Suppressed Airway Eosinophilia That Is Reversed by Granulocyte Macrophage Colony-Stimulating Factor

Abstract

In this study we investigated the impact of chronic allergen exposure on airway inflammation and humoral responses in sensitized mice. We observed marked eosinophilia in the bronchoalveolar lavage, lung tissue, and peripheral blood after 2 wk of exposure. In contrast, eosinophilia was markedly reduced by 3 wk and completely resolved by 4 wk of exposure, despite the continued presence of Ag. Decreases in airway eosinophilia were associated with a robust humoral response. We observed that levels of OVA-specific IgE, IgG1, and IgG2a increased during the course of exposure. To assess whether continuous exposure to Ag impacts the ability of the lung to respond to subsequent Ag challenge, mice were exposed to either 2 or 4 wk of OVA in the context of GM-CSF. All groups were then rested for 28 days and exposed to OVA on three consecutive days. We observed a significant decrease in airway eosinophilia and IL-5 expression in the bronchoalveolar lavage and serum in mice initially exposed to 4 wk of OVA, compared with animals exposed to 2 wk only. However, in both groups expression of B7.2 on dendritic cells as well as CD25, CD69, and T1/ST2 on CD4+ T cells was enhanced, suggesting immune activation. Delivery of rGM-CSF fully restored airway eosinophilia. This study shows that exposure to innocuous Ag alone does not lead to persistent eosinophilic airway inflammation, but rather to abrogated eosinophilia. This suppression can be reversed by GM-CSF.

Concurrent dual allergen exposure and its effects on airway hyperresponsiveness, inflammation and remodeling in mice

“…This suggests that HDM might be the allergen driving this aspect of the inflammatory response at 24 hours following the final allergen exposure. A possible explanation for the greater degree of eosinophilic inflammation in the HDM-exposed mice, compared with the OVA-exposed mice, might be that the protease activity of the HDM extracts gives this aeroallergen its antigenic nature and prevents the development of tolerance (Fattouh et al, 2005;Johnson et al, 2004;Kheradmand et al, 2002), which is known to occur with chronic exposure to OVA (Swirski et al, 2002;Swirski et al, 2006).…”

“…In addition, continuous exposure to OVA for several weeks in animals that have been sensitized previously with an aluminum-based adjuvant conjugated to OVA causes a decline in, and complete cessation of, the airway inflammatory response rather than an increase in, or maintenance of, the inflammation (Swirski et al, 2002;Swirski et al, 2006). Although it appears that the inflammatory aspect of the response in dual challenged animals may be explained entirely by the observed response to HDM alone, it is important to point out that exposure to HDM followed by exposure to OVA has been shown to prevent the tolerance associated with OVA alone (Fattouh et al, 2005).…”

Do the current house dust mite-driven models really mimic allergic asthma?

“…Chest radiographs were studied in all clinically presumptive cases, and only radiologically confirmed CAP cases were included in the analyses. The incidence of CAP was 36 per 1,000 per yr for ,5 yrs and 16 per 1,000 per yr for 5-15-yr-old children [2]. 51% in the younger and 11% in the older age group were treated in hospital.…”

“…As part of the Savo Pneumonia Study performed in [1981][1982] in Eastern Finland [2,3], we also analysed risk factors for CAP in children aged 3 months to 15 yrs [4]. The design of the study was prospective and strictly population-based.…”

Intranasal Exposure of Mice to House Dust Mite Elicits Allergic Airway Inflammation via a GM-CSF-Mediated Mechanism

“…Importantly, the need to use those artifices when eliciting allergic sensitization and airway inflammation is due in large part to the nature of the Ag selected, OVA. Indeed, not only does passive respiratory exposure to OVA lead to inhalation tolerance (1)(2)(3)(4), but continuous exposure to OVA of an already sensitized animal results in a diminution and complete abrogation, not an increase or maintenance, of the airway inflammatory response (5). To extend our knowledge of asthmatic inflammation, at least within the basic experimental domain, it thus seemed imperative to explore immune-inflammatory responses to real-life aeroallergens.…”