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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Principles of prevention of infectious diseases have been known for several thousands of years. One of the most significant tools of infection prophylaxis is immunization. Vaccines containing thymus-dependent antigens produce massive and complex immune response and feature immunologic memory. That is why they can successfully protect patients with diabetes. Lately, it has been thought by general public and even experts that application of vaccines within national immunization programmes is one of the etiopathogenetic factors in the development of type 1 diabetes mellitus (DM). However, analysis of extensive studies performed by the experts of the Institute for Vaccine Safety proved that there is no positive or negative impact of immunization on the development of type 1 diabetes mellitus. The basic vaccinations recommended for diabetics include immunizations against influenza, pneumococcal infections, tetanus and viral hepatitis B. Other vaccines are administered only after individual assessment of benefits and risks for the diabetic patient. Most often, these are vaccinations against viral hepatitis A, tick-borne encephalitis, meningococcal infections and other infections that put in risk diabetic patients travelling abroad.
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PMID:[Diabetes mellitus and immunization]. 1677 Oct 85

In the last decades of the 20th century, the incidence rate of type 1 diabetes increased in affluent countries. The pattern of occurrence of this autoimmune disease over time could provide helpful information to discriminate between alternative aetiologic hypotheses. In addition to genetic disposition, the incidence of type 1 diabetes seems to be conditioned by environmental factors and lifestyle. One theory proposes that the increase in the prevalence of autoimmune diseases is a result of the decrease in the incidence of childhood infections. To investigate the relationship between the incidence of type 1 diabetes and the decline of infectious diseases, we calculated the correlation between the occurrence of type 1 diabetes and tuberculosis in several European and non-European countries. The results of our analysis demonstrate an inverse correlation between the occurrences of type 1 diabetes and tuberculosis. A possible interpretation of this negative association is that a high socio-economic status and a westernised way of life imply a reduced or delayed exposure to infectious agents and so a reduced or delayed "pressure" on the immune system, which is free to mount inappropriate responses against self-antigens, as happens in type 1 diabetes.
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PMID:Negative association between occurrence of type 1 diabetes and tuberculosis incidence at population level. 1686 28

Infection, commencing across a wide age range, with a live, attenuated strain of Salmonella typhimurium, will halt the development of type 1 diabetes in the NOD mouse. The protective mechanism appears to involve the regulation of autoreactive T cells in a manner associated with long lasting changes in the innate immune compartment of these mice. We show in this study that autoreactive T cell priming and trafficking are altered in mice that have been infected previously by S. typhimurium. These changes are associated with sustained alterations in patterns of chemokine expression. We find that small numbers of dendritic cells from mice that have been previously infected with, but cleared all trace of a S. typhimurium infection are able to prevent the development of diabetes in the highly synchronized and aggressive cyclophosphamide-induced model. The effects we observe on autoreactive T cell trafficking are recapitulated by the immunomodulatory dendritic cell transfers in the cyclophosphamide model.
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PMID:Salmonella typhimurium infection in nonobese diabetic mice generates immunomodulatory dendritic cells able to prevent type 1 diabetes. 1688 82

Enterovirus (EV) infections have been associated with the pathogenesis of type 1 diabetes (T1D). They may cause beta-cell destruction either by cytolytic infection of the cells or indirectly by triggering the autoimmune response. Evidence for EV involvement have been presented in several studies, EV-IgM antibodies have been reported in T1D patients, EV-RNA has been found in the blood from T1D patients at onset, and EV have been isolated from newly diagnosed T1D. Our aim was to study infections with EV isolates from newly diagnosed T1D patients in human pancreatic islets in vitro. Two of them (T1 and T2) originated from a mother and her son diagnosed with T1D on the same day, the other two (A and E) were isolated from a pair of twins at the time of diagnosis of T1D in one of them. Isolated human pancreatic islets were infected and viral replication, viability and degree of cytolysis as well as insulin release in response to high glucose were measured. All four EV isolates replicated in the islet cells and virus particles and virus-induced vesicles were seen in the cytoplasm of the beta-cells. The isolates varied in their ability to induce cytolysis and to cause destruction of the islets and infection with two of the isolates (T1 and A) caused more pronounced destruction of the islets. Infection with the isolate from the healthy twin boy (E) was the least cytolytic. The ability to secrete insulin in response to high glucose was reduced in all infected islets as early as 3 days post infection, before any difference in viability was observed. To conclude, strains of EV isolated from T1D patients at clinical presentation of T1D revealed beta-cell tropism, and clearly affected the function of the beta-cell. In addition, the infection caused a clear increase in the number of dead cells.
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PMID:Effects on isolated human pancreatic islet cells after infection with strains of enterovirus isolated at clinical presentation of type 1 diabetes. 1716 56

Coxsackie B viruses (CVB) and Echoviruses (EV) form a single species; Human enterovirus B (HeV-B), within the genus Enterovirus. Although HeV-B infections are usually mild or asymptomatic, they can cause serious acute illnesses. In addition, HeV-B infections have been associated with chronic immune disorders, such as type 1 diabetes mellitus and chronic myocarditis/dilated cardiomyopathy. It has therefore been suggested that these viruses may trigger an autoimmune process. Here, we demonstrate that human dendritic cells (DCs), which play an essential role in orchestration of the immune response, are productively infected by EV, but not CVB strains, in vitro. Infection does not result in DC activation or the induction of antiviral immune responses. Instead, EV infection rapidly impedes Toll-like receptor-mediated production of cytokines and upregulation of maturation markers, and ultimately causes loss of DC viability. These results describe for the first time the effect of EV on the function and viability of human DCs and suggest that infection of DCs in vivo can impede regulation of immune responses.
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PMID:Echovirus infection causes rapid loss-of-function and cell death in human dendritic cells. 1729 95

beta-Cell replacement therapy via islet transplantation is a promising possibility for the optimal treatment of type 1 diabetes; however, such an approach is severely limited by the shortage of donor organs. This problem could be overcome if it were possible to generate transplantable islets from stem cells. We showed previously that adult beta-cells might originate from duct or duct-associated cells. Ductal progenitor cells in the pancreas would become particularly useful for therapies that target beta-cell replacement in diabetic patients, because duct cell types are abundantly available in the pancreas of these patients and in donor organs. In this study, we examined which embryonic transcription factors in adult mouse and human duct cells could efficiently induce their differentiation into insulin-expressing cells. Infection with the adenovirus expressing PDX-1, Ngn3, NeuroD, or Pax4 induced the insulin gene expression. NeuroD was the most effective inducer of insulin expression in primary duct cells. Surprisingly, adenovirus Pax4 strongly induced Ngn3 expression, while Pax4 is considered the downstream target of Ngn3. These data suggest that the overexpression of transcription factors, especially NeuroD, facilitates pancreatic stem/progenitor cell differentiation into insulin-producing cells.
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PMID:Induction of pancreatic stem/progenitor cells into insulin-producing cells by adenoviral-mediated gene transfer technology. 1729 98

Positional cloning of the underlying genes for the rare syndrome autoimmune polyendocrinopathy candidadiasis extrodermal dystrophy (APECED) opened a new venue of research on the role of central tolerance in autoimmunity. The associated autoimmune regulator gene (AIRE), was found to be expressed in medullary thymus epithelial cells (mTEC) in both man and mice, and to control promiscuous expression of sets of self antigens. The lack of AIRE in both mice and man led to the development of a quite specific, but also an inter-individual variable, set of autoimmune and infectious diseases. An article in this issue of the European Journal of Immunology demonstrates that several autoantigens controlled by AIRE are variably expressed in different human individuals. Most importantly it is shown that carriers of the type 1 diabetes (T1D) associated locus IDDM2 show lower expression of insulin in mTEC, as controlled by AIRE. The genetic variability of autoantigen expression in the thymus thus seems to determine the variable predisposition to autoimmunity.
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PMID:Aire-ing self antigen variability and tolerance. 1732 15

The objective of the study was to evaluate the association between infectious diseases and other events pertaining to childhood medical history and type 1 diabetes. A case-control study was carried out, taking as cases 159 type 1 diabetic patients (0-29 years) recorded from 1988 to 2000 within the population registry of the Pavia province (North Italy). As controls 318 non-diabetic subjects were matched by age and sex. A questionnaire was administered by standardised interviewers. Data were analysed by conditional logistic regression. Viral childhood diseases (OR 4.29; 95%CI 1.57-11.74) and bottle feeding (OR 1.83; 95%CI 1.08-3.09) were directly correlated to type 1 diabetes; an inverse correlation was found for vitamin D administration during lactation (0-14 years) (OR 0.31; 95%CI 0.11-0.86) and for history of scarlet fever in both sexes and age groups (OR 0.19; 95%CI 0.08-0.46). Most associations of the studied variables confirm already known findings. The significant inverse correlation of type 1 diabetes with scarlet fever history is a peculiar finding, the meaning of which is still obscure, although it has been recently described that streptococcal A infections are regulated by HLA class II alleles.
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PMID:Major childhood infectious diseases and other determinants associated with type 1 diabetes: a case-control study. 1735 80

Type 1 diabetes is characterized by T cell-mediated autoimmune destruction of pancreatic beta cells. Several studies have suggested an association between Coxsackie enterovirus seroconversion and onset of disease. However, a direct link between beta cell viral infection and islet inflammation has not been established. We analyzed pancreatic tissue from six type 1 diabetic and 26 control organ donors. Immunohistochemical, electron microscopy, whole-genome ex vivo nucleotide sequencing, cell culture, and immunological studies demonstrated Coxsackie B4 enterovirus in specimens from three of the six diabetic patients. Infection was specific of beta cells, which showed nondestructive islet inflammation mediated mainly by natural killer cells. Islets from enterovirus-positive samples displayed reduced insulin secretion in response to glucose and other secretagogues. In addition, virus extracted from positive islets was able to infect beta cells from human islets of nondiabetic donors, causing viral inclusions and signs of pyknosis. None of the control organ donors showed signs of viral infection. These studies provide direct evidence that enterovirus can infect beta cells in patients with type 1 diabetes and that infection is associated with inflammation and functional impairment.
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PMID:Coxsackie B4 virus infection of beta cells and natural killer cell insulitis in recent-onset type 1 diabetic patients. 1736 Mar 38

Solute carrier family 11 member a1 (Slc11a1; formerly Nramp1) encodes a late endosomal/lysosomal protein/divalent cation transporter that regulates iron homeostasis in macrophages. During macrophage activation, Slc11a1 has multiple pleiotropic effects on gene regulation and function, including gamma interferon-induced class II expression and antigen-presenting cell function. The wild-type allele at Slc11a1 has been associated with a bias in Th1 cell function in vivo, which is beneficial in resistance to infection against intracellular macrophage pathogens but detrimental in contributing to development of type 1 diabetes. The extent to which this depends on macrophage versus dendritic cell (DC) function is not known. Here we show that Slc11a1 is expressed in late endosomes and/or lysosomes of CD11c(+) DCs. DCs from mutant and congenic wild-type mice upregulate interleukin-12 (IL-12) and IL-10 mRNA in response to lipopolysaccharide (LPS) stimulation, but the ratio of IL-10 to IL-12 is higher in unstimulated DCs and DCs stimulated for 15 h with LPS from mutant mice than from wild-type mice. DCs from wild-type mice upregulate major histocompatibility complex class II in response to LPS more efficiently than DCs from mutant mice. Unstimulated DCs from wild-type and mutant mice present ovalbumin (OVA) peptide with an efficiency equivalent to that of an OVA-specific CD4 T-cell line, but DCs from wild-type mice are more efficient at processing and presenting OVA or Leishmania activator of cell kinase (LACK) protein to OVA- and LACK-specific T cells. These data indicate that wild-type Slc11a1 expressed in DCs may play a role both in determining resistance to infectious disease and in susceptibility to autoimmune disease such as type 1 diabetes.
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PMID:Slc11a1, formerly Nramp1, is expressed in dendritic cells and influences major histocompatibility complex class II expression and antigen-presenting cell function. 1762 Mar 57


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