Lamina propria macrophage phenotypes in relation to Escherichia coli in Crohn's disease

Background: Abnormal handling of E. coli by lamina propria (LP) macrophages may contribute to Crohn’s disease (CD) pathogenesis. We aimed to determine LP macrophage phenotypes in CD, ulcerative colitis (UC) and healthy controls (HC), and in CD, to compare macrophage phenotypes according to E. coli carriage. Methods: Mucosal biopsies were taken from 35 patients with CD, 9 with UC and 18 HCs. Laser capture microdissection was used to isolate E. coli-laden and unladen LP macrophages from ileal or colonic biopsies. From these macrophages, mRNA was extracted and cytokine and activation marker expression measured using RT-qPCR. Results: E. coli-laden LP macrophages were identified commonly in mucosal biopsies from CD patients (25/35, 71 %), rarely in UC (1/9, 11 %) and not at all in healthy controls (0/18). LP macrophage cytokine mRNA expression was greater in CD and UC than healthy controls. In CD, E. coli-laden macrophages expressed high IL-10 & CD163 and lower TNFα, IL-23 & iNOS irrespective of macroscopic inflammation. In inflamed tissue, E. coli-unladen macrophages expressed high TNFα, IL-23 & iNOS and lower IL-10 & CD163. In uninflamed tissue, unladen macrophages had low cytokine mRNA expression, closer to that of healthy controls. Conclusion: In CD, intra-macrophage E. coli are commonly found and LP macrophages express characteristic cytokine mRNA profiles according to E. coli carriage. Persistence of E. coli within LP macrophages may provide a stimulus for chronic inflammation

Correlates of fear of hypoglycemia among patients with type 1 and 2 diabetes mellitus in outpatient hospitals in Zambia

Background: Severe hypoglycemia is a burdensome complication of diabetes mellitus that can induce fear of hypoglycemia and contribute to suboptimal glycemic control. The challenge is to achieve and maintain adequate glycemic control while avoiding episodes of severe hypoglycemia. The purpose of the study was to determine how common fear of hypoglycemia was in Zambian out-patients with diabetes and also to explore correlates of fear of hypoglycemia. Methods: One hundred fifty-seven individuals with types 1 and 2 diabetes participated in the study. Fear of Hypoglycemia Scale, Diabetes Self-Care Inventory, Problem Areas in Diabetes, and the Major Depression Inventory were completed. Multiple linear regression models were computed to assess the association between fear of hypoglycemia and psychological factors. Results: About 19% [16.3% type 1 and 12.6% type 2] of individuals with diabetes based on item endorsement expressed fear of hypoglycemia especially among individuals with type 1 diabetes. After controlling for demographic variables, diabetes self-care (ß = 0.24, p \u3c 0.05), and diabetes specific distress (ß = 0.41, p \u3c 0.001) were associated with fear of hypoglycemia. Conclusion: Fear of hypoglycemia was common and was positively associated with diabetes specific emotional distress and diabetes self-care. Interventions to avert fear of hypoglycemia are needed while optimizing glycemic control through managing diabetes care and emotion distress in individuals with diabetes

IBD—what role do Proteobacteria play?

The gastrointestinal microbiota has come to the fore in the search for the causes of IBD. This shift has largely been driven by the finding of genetic polymorphisms involved in gastrointestinal innate immunity (particularly polymorphisms in NOD2 and genes involved in autophagy) and alterations in the composition of the microbiota that might result in inflammation (so-called dysbiosis). Microbial diversity studies have continually demonstrated an expansion of the Proteobacteria phylum in patients with IBD. Individual Proteobacteria, in particular (adherent-invasive) Escherichia coli, Campylobacter concisus and enterohepatic Helicobacter, have all been associated with the pathogenesis of IBD. In this Review, we comprehensively describe the various associations of Proteobacteria and IBD. We also examine the importance of pattern recognition in the extracellular innate immune response of the host with particular reference to Proteobacteria, and postulate that Proteobacteria with adherent and invasive properties might exploit host defenses, drive proinflammatory change, alter the intestinal microbiota in favor of dysbiosis and ultimately lead to the development of IBD

Intruders below the Radar: Molecular Pathogenesis of Bartonella spp

Summary: Bartonella spp. are facultative intracellular pathogens that employ a unique stealth infection strategy comprising immune evasion and modulation, intimate interaction with nucleated cells, and intraerythrocytic persistence. Infections with Bartonella are ubiquitous among mammals, and many species can infect humans either as their natural host or incidentally as zoonotic pathogens. Upon inoculation into a naive host, the bartonellae first colonize a primary niche that is widely accepted to involve the manipulation of nucleated host cells, e.g., in the microvasculature. Consistently, in vitro research showed that Bartonella harbors an ample arsenal of virulence factors to modulate the response of such cells, gain entrance, and establish an intracellular niche. Subsequently, the bacteria are seeded into the bloodstream where they invade erythrocytes and give rise to a typically asymptomatic intraerythrocytic bacteremia. While this course of infection is characteristic for natural hosts, zoonotic infections or the infection of immunocompromised patients may alter the path of Bartonella and result in considerable morbidity. In this review we compile current knowledge on the molecular processes underlying both the infection strategy and pathogenesis of Bartonella and discuss their connection to the clinical presentation of human patients, which ranges from minor complaints to life-threatening disease