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It is now well established that passive exposure to inhaled OVA leads to a state of immunological tolerance. Therefore, to elicit allergic sensitization, researchers have been compelled to devise alternative strategies, such as the systemic delivery of OVA in the context of powerful adjuvants, which are alien to the way humans are exposed and sensitized to(More)
The purpose of this study was to investigate the impact of mainstream cigarette smoke exposure (MTS) on allergic sensitization and the development of allergic inflammatory processes. Using two different experimental murine models of allergic airways inflammation, we present evidence that MTS increased cytokine production by splenocytes in response to OVA(More)
It is now fully appreciated that asthma is a disease of a chronic nature resulting from intermittent or continued aeroallergen exposure leading to airway inflammation. To investigate responses to continuous antigen exposure, mice were exposed to either house dust mite extract (HDM) or ovalbumin intranasally for five consecutive days, followed by 2 days of(More)
The impact of cigarette smoke on allergic asthma remains controversial both clinically and experimentally. The objective of this study was to investigate, in a murine model, how cigarette smoke affects immune inflammatory processes elicited by a surrogate allergen. In our experimental design, mice were concurrently exposed to cigarette smoke and ovalbumin(More)
OBJECTIVE The NOX2 NADPH oxidase complex produces reactive oxygen species and plays a critical role in the killing of microbes by phagocytes. Genetic mutations in genes encoding components of the complex result in both X-linked and autosomal recessive forms of chronic granulomatous disease (CGD). Patients with CGD often develop intestinal inflammation that(More)
BACKGROUND & AIMS RAC1 is a guanosine triphosphatase that has an evolutionarily conserved role in coordinating immune defenses, from plants to mammals. Chronic inflammatory bowel diseases are associated with dysregulation of immune defenses. We studied the role of RAC1 in inflammatory bowel diseases using human genetic and functional studies and animal(More)
BACKGROUND & AIMS Very early onset inflammatory bowel diseases (VEOIBD), including infant disorders, are a diverse group of diseases found in children younger than 6 years of age. They have been associated with several gene variants. Our aim was to identify the genes that cause VEOIBD. METHODS We performed whole exome sequencing of DNA from 1 infant with(More)
Recent genetic-based studies have implicated a number of immune-related genes in the pathogenesis of inflammatory bowel disease (IBD). Our recent genetic studies showed that RAC2 is associated with human IBD; however, its role in disease pathogenesis is unclear. Given Rac2's importance in various fundamental immune cell processes, we investigated whether a(More)
The intracellular bacterial pathogen Listeria monocytogenes produces phospholipases C (PI-PLC and PC-PLC) and the pore-forming cytolysin listeriolysin O (LLO) to escape the phagosome and replicate within the host cytosol. We found that PLCs can also activate the phagocyte NADPH oxidase during L. monocytogenes infection, a response that would adversely(More)
House dust mite (HDM) is the most pervasive indoor aeroallergen source worldwide. Allergens derived from HDM are associated with sensitization and allergic asthma. Allergic asthma is an immunologically driven disease characterized by a Th2-polarized immune response, eosinophilic inflammation, airway hyperreactivity, and remodeling. Animal models of asthma(More)