Eosinophilia is induced in the colon of Th2-sensitized mice upon exposure to locally expressed antigen

Abstract

Eosinophilic inflammation is a feature of a variety of gastrointestinal (GI) disorders including eosinophil-associated GI disorder, allergy, inflammatory bowel disease, and parasite infection. Elucidating the mechanisms of eosinophil infiltration into the GI tract is important to the understanding of multiple disease processes. We hypothesize that eosinophilia in the large intestine (colon) can be induced by an antigen in a host that is associated with Th2-skewed antigen-specific immune responses. To investigate the importance of antigenic triggering, we established polarized antigen-specific Th2 type responses in BALB/c mice, using ovalbumin in conjunction with aluminum hydroxide. Upon challenge at the colonic mucosa through transient (3-4 days) expression of the antigen gene encoded in an adenovirus vector, sensitized animals developed significant subepithelial colonic inflammation, characterized by marked eosinophilic infiltration, and the presence of enlarged and increased numbers of lymphoid follicles. The alterations peaked around day 5 and resolved over the next 5-10 days, and no epithelial cell damage was detected through the entire course. Administration of a control (empty) adenovirus vector did not lead to any pathological changes. These data suggest that colonic eosinophilia can be induced by exposure to an antigen associated with preexisting Th2-skewed responses. Thus the model established here may provide a useful tool to study GI and, in particular, colonic inflammation with respect to underlying mechanisms involved in the recruitment and the immediate function of eosinophils.

Oral vaccines

“…4,21,22 Antigen challenge through the nose of animals pre-sensitized to the same antigen induced eosinophilia in the lung but not in the intestine. 23 As shown in our recent study, 11 oral immunization with nanoparticles that target the large intestinal mucosa did not induce immune responses in the small intestine while immunization targeting the small intestine failed to elicit the large intestinal immune responses as well. These discriminations may result from the differences in specialized anatomical and immunological features of the intestinal wall 24 or the presence of and gut interaction with commensal bacteria in the lumen.…”

Potential for Early-Life Immune Insult Including Developmental Immunotoxicity in Autism and Autism Spectrum Disorders: Focus on Critical Windows of Immune Vulnerability

“…The Th-2 driven allergic component has been reported as an eosinophilia found in autistic children with gluten sensitivity (Ashwood et al, 2003(Ashwood et al, , 2004. Zhu et al (2007) recently described the role of eosinophil infiltration in the gut of sensitized mice. As reviewed in , pediatric autistic patients maintained on gluten-free diets exhibited a reduced number of eosinophils upon biopsy (Ashwood et al, 2003).…”

Comprehensive transcriptional profiling of aging porcine liver

“…Aging significantly affects a number of physiological and biochemical functions that are performed by the liver (Kitani, 1994). Aging has been suggested as a major risk factor for the development of various diseases (Rodwell et al, 2002), and several studies showed that aging increased the risks for numerous liver diseases that cause an increase in the mortality rate (Amarapurkar et al, 2007; Regev & Schiff, 2001; Sheedfar et al, 2013). Previous studies have shown that the liver size progressively decreased in response to aging and a marked decline in volume was found to occur above the age of 60 years in humans (Woodhouse & James, 1990).…”