<i>Salmonella typhimurium</i> Infection in Nonobese Diabetic Mice Generates Immunomodulatory Dendritic Cells Able to Prevent Type 1 Diabetes

Raine, Tim; Zaccone, Paola; Mastroeni, Pietro; Cooke, Anne

doi:10.4049/jimmunol.177.4.2224

Cited by 38 publications

(31 citation statements)

References 51 publications

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“…H. polygyrus-infected mice showed an increase in OX6 on May 9, 2018 by guest http://iai.asm.org/ expression at both time points. CD62L (L-selectin) is lost from T cells upon antigen activation, and thymus-derived naturally arising CD4 ϩ regulatory T cells have been shown to express high levels of CD62L and CD25 (28,38). Other populations of CD4 ϩ regulatory T cells have been described that can be induced following exposure to IL-10 and antigen, and these induced T regulatory cells may be found in both the CD25 ϩ and CD25…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Autoimmune Type 1 Diabetes by Gastrointestinal Helminth Infection

et al. 2007

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Gastrointestinal nematode infections are prevalent worldwide and are potent inducers of T helper 2 responses with the capacity to modulate the immune response to heterologous antigens. Parasitic helminth infection has even been shown to modulate the immune response associated with autoimmune diseases. Nonobese diabetic (NOD) mice provide a model for studying human autoimmune diabetes; as in humans, the development of diabetes in NOD mice has been linked to the loss of self-tolerance to beta cell autoantigens. Previous studies with the NOD mouse have shown that helminth and bacterial infection appears to inhibit type 1 diabetes by disrupting the pathways leading to the Th1-mediated destruction of insulin-producing beta cells. The aim of our study was to examine whether infection with the gastrointestinal helminths Trichinella spiralis or Heligmosomoides polygyrus could inhibit the development of autoimmune diabetes in NOD mice and to analyze the mechanisms involved in protection and the role of Th2 responses. Protection from diabetes was afforded by helminth infection, appeared to inhibit autoimmune diabetes by disrupting pathways leading to the destruction of beta cells, and was mediated by seemingly independent mechanisms depending on the parasite but which may be to be related to the capacity of the host to mount a Th2 response.

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Section: Resultsmentioning

confidence: 99%

Inhibition of Autoimmune Type 1 Diabetes by Gastrointestinal Helminth Infection

et al. 2007

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“…infection with attenuated Salmonella enteriditis serotype typhimurium (Salmonella typhimurium) halted type 1 diabetes onset in NOD mice [38]. These differences in the impact on type 1 diabetes development may reflect that intestinal barrier disruption (as seen with C. rodentium infection) does not occur when Salmonella typhimurium is administered parenterally and suggests that disruption of the gut barrier contributes to pathogenaccelerated insulitis.…”

Section: Discussionmentioning

confidence: 99%

Gut barrier disruption by an enteric bacterial pathogen accelerates insulitis in NOD mice

et al. 2009

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Aims/hypothesis Increased exposure to enteric microbes as a result of intestinal barrier disruption is thought to contribute to the development of several intestinal inflammatory diseases; however, it less clear whether such exposure modulates the development of extra-intestinal inflammatory and autoimmune diseases. The goal of this study was to examine the potential role of pathogenic enteric microbes and intestinal barrier dysfunction in the pathogenesis of type 1 diabetes. Methods Using NOD mice, we assessed: (1) intrinsic barrier function in mice at different ages by measuring serum levels of FITC-labelled dextran; and (2) the impact on insulitis development of infection by strains of an enteric bacterial pathogen (Citrobacter rodentium) either capable (wild-type) or incapable (lacking Escherichia coli secreted protein F virulence factor owing to deletion of the gene [ΔespF]) of causing intestinal epithelial barrier disruption. Results Here we demonstrate that prediabetic (12-weekold) NOD mice display increased intestinal permeability compared with non-obese diabetes-resistant and C57BL/6 mice. We also found that young (4-week-old) NOD mice infected with wild-type C. rodentium exhibited accelerated development of insulitis in concert with infection-induced barrier disruption. In contrast, insulitis development was not altered in NOD mice infected with the non-barrier-disrupting ΔespF strain. Moreover, C. rodentium-infected NOD mice demonstrated increased activation and proliferation of pancreatic-draining lymph node T cells, including diabetogenic CD8 + T cells, compared with uninfected NOD mice. Conclusions/interpretation This is the first demonstration that a loss of intestinal barrier integrity caused by an enteric bacterial pathogen results in the activation of diabetogenic CD8 + T cells and modulates insulitis.

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“…In order to assess whether a small proportion of IFN-γ producers could selectively expand in the NOD environment, we "spiked" a Th17 inoculum with a 1% Th1 contaminant of Th1-polarized BDC2.5 cells. These cells could be identified in vivo, because they were derived from a BDC2.5NOD strain, expressing GFP on its T cells (17). Nevertheless, although we could detect the GFP Th1 cells in PLNs and pancreata of these mice, they had not expanded significantly beyond the ratio in which they had been transferred and were unable to induce diabetes if transferred in these low numbers on their own (Figure 3).…”

Section: Th17 Bdc25 Cells Transfer Diabetes With a Similar Kinetic Tomentioning

confidence: 94%

Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice

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et al. 2009

J. Clin. Invest.

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Salmonella typhimurium Infection in Nonobese Diabetic Mice Generates Immunomodulatory Dendritic Cells Able to Prevent Type 1 Diabetes

Cited by 38 publications

References 51 publications

Inhibition of Autoimmune Type 1 Diabetes by Gastrointestinal Helminth Infection

Inhibition of Autoimmune Type 1 Diabetes by Gastrointestinal Helminth Infection

Gut barrier disruption by an enteric bacterial pathogen accelerates insulitis in NOD mice

Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice

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