Increased Recruitment but Impaired Function of Leukocytes during Inflammation in Mouse Models of Type 1 and Type 2 Diabetes

BACKGROUND: Patients suffering from diabetes show defective bacterial clearance. This study investigates the effects of elevated plasma glucose levels during diabetes on leukocyte recruitment and function in established models of inflammation. METHODOLOGY/PRINCIPAL FINDINGS: Diabetes was induced in C57Bl/6 mice by intravenous alloxan (causing severe hyperglycemia), or by high fat diet (moderate hyperglycemia). Leukocyte recruitment was studied in anaesthetized mice using intravital microscopy of exposed cremaster muscles, where numbers of rolling, adherent and emigrated leukocytes were quantified before and during exposure to the inflammatory chemokine MIP-2 (0.5 nM). During basal conditions, prior to addition of chemokine, the adherent and emigrated leukocytes were increased in both alloxan- (62±18% and 85±21%, respectively) and high fat diet-induced (77±25% and 86±17%, respectively) diabetes compared to control mice. MIP-2 induced leukocyte emigration in all groups, albeit significantly more cells emigrated in alloxan-treated mice (15.3±1.0) compared to control (8.0±1.1) mice. Bacterial clearance was followed for 10 days after subcutaneous injection of bioluminescent S. aureus using non-invasive IVIS imaging, and the inflammatory response was assessed by Myeloperoxidase-ELISA and confocal imaging. The phagocytic ability of leukocytes was assessed using LPS-coated fluorescent beads and flow cytometry. Despite efficient leukocyte recruitment, alloxan-treated mice demonstrated an impaired ability to clear bacterial infection, which we found correlated to a 50% decreased phagocytic ability of leukocytes in diabetic mice. CONCLUSIONS/SIGNIFICANCE: These results indicate that reduced ability to clear bacterial infections observed during experimentally induced diabetes is not due to reduced leukocyte recruitment since sustained hyperglycemia results in increased levels of adherent and emigrated leukocytes in mouse models of type 1 and type 2 diabetes. Instead, decreased phagocytic ability observed for leukocytes isolated from diabetic mice might account for the impaired bacterial clearance

How the religious cleavages of civil society shape national identity

This article focuses on religion and the embeddedness in civil society. We examine the relationship between religion and national identity (ethnic and civic). Our findings show that individual religiosity continues to play an important role in sustaining both forms of national identity. In addition to other studies, we examine the relationship between religion as a societal phenomenon and individual national identity and find the following: The stronger the relationship between state and religion, the stronger the ethnic identity; the more the religious homogeneity, the stronger the ethnic identity; and there is no relationship between aggregated degree of religious organizations and identity. We conclude that religion continues to play a major role in the making of civil society, but the specific circumstances vary according to the religious representation. In other words, religion can both make and unmake national identity. The associational life of civil society is the actual ground where all versions of the good are worked out and tested . . . and proven to be partial, incomplete, ultimately unsatisfying. It can’t be the case that living on this ground is good-in-itself; there isn’t any other place to live. What is true is that the quality of our political and economic activity and of our national culture is intimately connected to the strength and vitality of our associations. Ideally, civil society is a setting of settings: all are included, none is preferred