Abstract
Allergens are molecules that elicit a hypersensitive inflammatory response in sensitized individuals and are derived from a variety of sources. Alt a 1 is the most clinically important secreted allergen of the ubiquitous fungus, Alternaria. It has been shown to be a major allergen causing IgE-mediated allergic response in the vast majority of Alternaria-sensitized individuals. However, no studies have been conducted in regards to the innate immune eliciting activities of this clinically relevant protein. In this study, recombinant Alt a 1 was produced, purified, labeled, and incubated with BEAS-2B, NHBE, and DHBE human lung epithelial cells. Alt a 1 elicited strong induction of IL-8, MCP-1, and Gro-a/b/g. Using gene-specific siRNAs, blocking antibodies, and chemical inhibitors such as LPS-RS, it was determined that Alt a 1-induced immune responses were dependent upon toll-like receptors (TLRs) 2 and 4, and the adaptor proteins MYD88 and TIRAP. Studies utilizing human embryonic kidney cells engineered to express single receptors on the cell surface such as TLRs, further confirmed that Alt a 1-induced innate immunity is dependent upon TLR4 and to a lesser extent TLR2.
Highlights
Besides being a common cause of allergic rhinitis, sensitivity to the airborne fungus Alternaria alternata is believed to be a common cause of allergic/atopic asthma
Our results indicated that Alt a 1 induced the secretion of several cytokines and chemokines in BEAS-2B human bronchial epithelial airway cells—primarily MCP-1 (CCL2), IL-8, and GROa/b/g (CXCL1/2/3) (Figure 1)
The goal of this experiment was to characterize the temporal aspects of IL-8 secretion and to determine if 24 h post treatment was optimal for supernatant collection
Summary
Besides being a common cause of allergic rhinitis, sensitivity to the airborne fungus Alternaria alternata is believed to be a common cause of allergic/atopic asthma. Alternaria sensitivity has been shown to be a risk factor for asthma but can directly lead to the development of severe and potentially fatal asthma often more than any other fungus [1,2,3,4,5]. It has long been speculated that this type of exposure may be partially responsible for both the chronic nature and severity of asthma in Alternaria-sensitized individuals [9]. In a survey by the National Institute of Environmental Health & Safety of 831 homes, containing 2,456 individuals, it was found that the prevalence of current symptomatic asthma correlated with increasing indoor Alternaria concentrations [3]. Higher levels of Alternaria antigens in the environment significantly increased odds of having had asthma symptoms during the preceding year, more so than other examined antigens
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