Remote allergen exposure elicits eosinophil infiltration into allergen nonexposed mucosal organs and primes for allergic inflammation.

The natural history of allergic diseases suggests bidirectional and progressive relationships between allergic disorders of the skin, lung, and gut indicative of mucosal organ crosstalk. However, impacts of local allergic inflammation on the cellular landscape of remote mucosal organs along the skin:lung:gut axis are not yet known. Eosinophils are tissue-dwelling innate immune leukocytes associated with allergic diseases. Emerging data suggest heterogeneous phenotypes of tissue-dwelling eosinophils contribute to multifaceted roles that favor homeostasis or disease. This study investigated the impact of acute local allergen exposure on the frequency and phenotype of tissue eosinophils within remote mucosal organs. Our findings demonstrate allergen challenge to skin, lung, or gut elicited not only local eosinophilic inflammation, but also increased the number and frequency of eosinophils within remote, allergen nonexposed lung, and intestine. Remote allergen-elicited lung eosinophils exhibited an inflammatory phenotype and their presence associated with enhanced susceptibility to airway inflammation induced upon subsequent inhalation of a different allergen. These data demonstrate, for the first time, a direct effect of acute allergic inflammation on the phenotype and frequency of tissue eosinophils within antigen nonexposed remote mucosal tissues associated with remote organ priming for allergic inflammation.

Resident intestinal eosinophils constitutively express antigen presentation markers and include two phenotypically distinct subsets of eosinophils.

Intestinal eosinophils are implicated in homeostatic and disease-associated processes, yet the phenotype of intestinal tissue-dwelling eosinophils is poorly defined and their roles in intestinal health or disease remain enigmatic. Here we probed the phenotype and localization of eosinophils constitutively homed to the small intestine of naive mice at baseline, and of antigen-sensitized mice following intestinal challenge. Eosinophils homed to the intestinal lamina propria of naive mice were phenotypically distinguished from autologous blood eosinophils, and constitutively expressed antigen-presenting cell markers, suggesting that intestinal eosinophils, unlike blood eosinophils, may be primed for antigen presentation. We further identified a previously unrecognized resident population of CD11chi eosinophils that are recovered with intraepithelial leucocytes, and that are phenotypically distinct from both lamina propria and blood eosinophils. To better visualize intestinal eosinophils in situ, we generated eosinophil reporter mice wherein green fluorescent protein expression is targeted to both granule-delimiting and plasma membranes. Analyses of deconvolved fluorescent z-section image stacks of intestinal tissue sections from eosinophil reporter mice revealed eosinophils within intestinal villi exhibited dendritic morphologies with cellular extensions that often contacted the basement membrane. Using an in vivo model of antigen acquisition in antigen-sensitized mice, we demonstrate that both lamina propria-associated and intraepithelium-associated eosinophils encounter, and are competent to acquire, lumen-derived antigen. Taken together these data provide new foundational insights into the organization and functional potential of intestinal tissue-dwelling eosinophils, including the recognition of different subsets of resident intestinal eosinophils, and constitutive expression of antigen-presenting cell markers.

Experiences of People with Diabetes by Payer Type: An Analysis of the Roper Diabetes Data Set.

INTRODUCTION: The study details the experiences of Medicare, Medicaid and privately insured patients with diabetes in the United States by focusing on how these distinct populations perceive their disease and manage their treatment. METHODS: A national survey was fielded among a representative sample of 2,307 US adult diagnosed diabetes patients to investigate demographic, lifestyle, treatment, access to information, and socioeconomic status. This was achieved using a combination of telephone-based interviews and internet-based questionnaires administered via KnowledgePanel®, the only large-scale online panel based on a representative random sample of the US population. RESULTS: Patients with Medicaid-based insurance face significant differences in diagnosis, treatment and intensity of their diabetes as compared to their Medicare and privately insured counterparts. Medicaid patients develop diabetes at an earlier age with an increased level of severity, and face significant socioeconomic concerns. Medicaid patients also have different health information seeking preferences than their counterparts, impacted by technology use patterns and education preferences. All groups report challenges in paying for their diabetes care, though cost-sharing requirements are relatively low. CONCLUSIONS: Significant variation in experience between Medicaid, Medicare, and privately insured patients can inform disease management and patient engagement strategies. Payers, clinicians and public health agencies can leverage these findings to design initiatives more effectively and understand how intergroup variability impacts program uptake and disease outcomes.

CCL11 elicits secretion of RNases from mouse eosinophils and their cell-free granules.

Rapid secretion of eosinophil-associated RNases (EARs), such as the human eosinophilic cationic protein (ECP), from intracellular granules is central to the role of eosinophils in allergic diseases and host immunity. Our knowledge regarding allergic inflammation has advanced based on mouse experimental models. However, unlike human eosinophils, capacities of mouse eosinophils to secrete granule proteins have been controversial. To study mechanisms of mouse eosinophil secretion and EAR release, we combined an RNase assay of mouse EARs with ultrastructural studies. In vitro, mouse eosinophils stimulated with the chemokine eotaxin-1 (CCL11) secreted enzymatically active EARs (EC(50) 5 nM) by piecemeal degranulation. In vivo, in a mouse model of allergic airway inflammation, increased airway eosinophil infiltration (24-fold) correlated with secretion of active RNases (3-fold). Moreover, we found that eosinophilic inflammation in mice can involve eosinophil cytolysis and release of cell-free granules. Cell-free mouse eosinophil granules expressed functional CCR3 receptors and secreted their granule proteins, including EAR and eosinophil peroxidase in response to CCL11. Collectively, these data demonstrate chemokine-dependent secretion of EARs from both intact mouse eosinophils and their cell-free granules, findings pertinent to understanding the pathogenesis of eosinophil-associated diseases, in which EARs are key factors.

Eosinophils: offenders or general bystanders in allergic airway disease and pulmonary immunity?

Eosinophils have long been noted to be present in asthma and other forms of pulmonary inflammation, but whether they act as true offenders or merely as bystanders has been a point of uncertainty. However, in recent years, there has been increasing evidence suggesting that eosinophils are not passive cells in the respiratory system, acting only as markers of allergic inflammation. This review discusses key evidence from animal models and human clinical trials that support the importance of eosinophils as active and necessary, rather than passive and unnecessary, to the pathogenesis of allergic airway disease. Analyses that are supportive of important immunoregulatory roles of eosinophils in allergic pulmonary inflammation are also reviewed. Data indicating that eosinophils contribute to viral, bacterial, and mycobacterial defense and clearance are detailed. Continually increasing evidence has supported a new conception of eosinophils as being multifaceted immune cells with complex interactions with other immune cells and their local environment.

Eosinophils in innate immunity: an evolving story.

Eosinophils are innate immune leukocytes found in relatively low numbers within the blood. Terminal effector functions of eosinophils, deriving from their capacity to release their content of tissue-destructive cationic proteins, have historically been considered primary effector mechanisms against specific parasites, and are likewise implicated in tissue damage accompanying allergic responses such as asthma. However, the past decade has seen dramatic advancements in the field of eosinophil immunobiology, revealing eosinophils to also be key participants in many other facets of innate immunity, from bridging innate and adaptive immune responses to orchestrating tissue remodeling events. Here, we review the multifaceted functions of eosinophils in innate immunity that are currently known, and discuss new avenues in this evolving story.