OdDHL Inhibits T Cell Subset Differentiation and Delays Diabetes Onset in NOD Mice

Gaisford, Wendy; Pritchard, David; Cooke, Anne

doi:10.1128/cvi.00032-11

Cited by 5 publications

(5 citation statements)

References 30 publications

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“…Small molecules/proteins isolated from the infectious agents have shown to account for these protective effects [94]. Previous studies indicated that P. aeruginosa QS signal OdDHL (viz.…”

Section: Reviewmentioning

confidence: 99%

“…3O-C 12 - HSL) could delay the onset of type 1 diabetes (T1D) in the non-obese diabetic (NOD) mouse model. Furthermore, using an antigen-presenting cell-free system, the authors showed that 3O-C 12 -HSL could not only inhibit the proliferation of naïve T cells but directly suppress the differentiation of T cell subsets; however, no effects was seen with 3O-C 12 -HSL on the inhibition of primed and committed differentiated T cell responses, suggesting that 3O-C 12 -HSL-mediated immune mechanism may be restricted to initial stages of infection [94]. …”

Section: Reviewmentioning

confidence: 99%

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Role of intestinal microbiota and metabolites on gut homeostasis and human diseases

2017

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BackgroundA vast diversity of microbes colonizes in the human gastrointestinal tract, referred to intestinal microbiota. Microbiota and products thereof are indispensable for shaping the development and function of host innate immune system, thereby exerting multifaceted impacts in gut health.MethodsThis paper reviews the effects on immunity of gut microbe-derived nucleic acids, and gut microbial metabolites, as well as the involvement of commensals in the gut homeostasis. We focus on the recent findings with an intention to illuminate the mechanisms by which the microbiota and products thereof are interacting with host immunity, as well as to scrutinize imbalanced gut microbiota (dysbiosis) which lead to autoimmune disorders including inflammatory bowel disease (IBD), Type 1 diabetes (T1D) and systemic immune syndromes such as rheumatoid arthritis (RA).ResultsIn addition to their well-recognized benefits in the gut such as occupation of ecological niches and competition with pathogens, commensal bacteria have been shown to strengthen the gut barrier and to exert immunomodulatory actions within the gut and beyond. It has been realized that impaired intestinal microbiota not only contribute to gut diseases but also are inextricably linked to metabolic disorders and even brain dysfunction.ConclusionsA better understanding of the mutual interactions of the microbiota and host immune system, would shed light on our endeavors of disease prevention and broaden the path to our discovery of immune intervention targets for disease treatment.

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“…Small molecules/proteins isolated from the infectious agents have shown to account for these protective effects [94]. Previous studies indicated that P. aeruginosa QS signal OdDHL (viz.…”

Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

Role of intestinal microbiota and metabolites on gut homeostasis and human diseases

2017

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“…We observed a significant decrease of diabetes incidence after IRT5 administration for 36 weeks, which was associated with reduced gut permeability and increased proportion of CCR9 + gut-tropic Treg cells. In this investigation, we started IRT5 administration at 4 weeks of age because previous studies showed that inhibition of physiological β-cell apoptosis at day 14–42 with benzyloxylcarbonyl-V-A- d - O -methyl fluoromethyl ketone (zVAD-fmk), a pan-caspase inhibitor, was able to inhibit sensitization to diabetogenic T cells ( 38 ) and immune intervention at 4 weeks of age could block the development of diabetes in NOD mice ( 39 – 41 ). We continued IRT5 treatment up to 40 weeks of age because diabetes developed even after 32–36 weeks of age in our NOD colonies ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

Amelioration of Autoimmune Diabetes of NOD Mice by Immunomodulating Probiotics

Kim

Lee²,

et al. 2020

Front. Immunol.

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Type 1 autoimmune diabetes is an autoimmune disease characterized by specific destruction of pancreatic β-cells producing insulin. Recent studies have shown that gut microbiota and immunity are closely linked to systemic immunity, affecting the balance between pro-inflammatory and regulatory immune responses. Altered gut microbiota may be causally related to the development of immune-mediated diseases, and probiotics have been suggested to have modulatory effects on inflammatory diseases and immune disorders. We studied whether a probiotic combination that has immunomodulatory effects on several inflammatory diseases can reduce the incidence of diabetes in non-obese diabetic (NOD) mice, a classical animal model of human T1D. When Immune Regulation and Tolerance 5 (IRT5), a probiotic combination comprising Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus reuteri, Bifidobacterium bifidium, and Streptococcus thermophiles, was administered 6 times a week for 36 weeks to NOD mice, beginning at 4 weeks of age, the incidence of diabetes was significantly reduced. Insulitis score was also significantly reduced, and β-cell mass was conversely increased by IRT5 administration. IRT5 administration significantly reduced gut permeability in NOD mice. The proportion of total regulatory T cells was not changed by IRT5 administration; however, the proportion of CCR9 + regulatory T (Treg) cells expressing gut-homing receptor was significantly increased in pancreatic lymph nodes (PLNs) and lamina propria of the small intestine (SI-LP). Type 1 T helper (Th1) skewing was reduced in PLNs by IRT5 administration. IRT5 could be a candidate for an effective probiotic combination, which can be safely administered to inhibit or prevent type 1 diabetes (T1D).

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“…N-(3-oxododecanoyl)-l-HSL(3-oxo-C12-HSL/OdDHL). 3-oxo-C12-HSL, a specific type of acyl homoserine lactone (AHL), is an auto-inducing, quorum-sensing associated virulence factor that regulates swarming, toxin and protease production, and proper biofilm formation [ 115 , 116 ]. OdDHL inhibits naive T-Cell proliferation as well as subtype differentiation.…”

Section: Description Of Targetsmentioning

confidence: 99%

“…It also decreases antibody production at high concentrations and promotes IgE/IL-4 at low concentrations. OdDHL also regulates Las gene expression, most notably LasR, and upregulates IL-8 in corneal infections [ 115 , 116 ]. Additionally, it has been shown to inhibit dendritic cell concentrations in a dose-dependent fashion.…”

Section: Description Of Targetsmentioning

confidence: 99%

Potential Therapeutic Targets for Combination Antibody Therapy against Pseudomonas aeruginosa Infections

et al. 2021

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Despite advances in antimicrobial therapy and even the advent of some effective vaccines, Pseudomonas aeruginosa (P. aeruginosa) remains a significant cause of infectious disease, primarily due to antibiotic resistance. Although P. aeruginosa is commonly treatable with readily available therapeutics, these therapies are not always efficacious, particularly for certain classes of patients (e.g., cystic fibrosis (CF)) and for drug-resistant strains. Multi-drug resistant P. aeruginosa infections are listed on both the CDC’s and WHO’s list of serious worldwide threats. This increasing emergence of drug resistance and prevalence of P. aeruginosa highlights the need to identify new therapeutic strategies. Combinations of monoclonal antibodies against different targets and epitopes have demonstrated synergistic efficacy with each other as well as in combination with antimicrobial agents typically used to treat these infections. Such a strategy has reduced the ability of infectious agents to develop resistance. This manuscript details the development of potential therapeutic targets for polyclonal antibody therapies to combat the emergence of multidrug-resistant P. aeruginosa infections. In particular, potential drug targets for combinational immunotherapy against P. aeruginosa are identified to combat current and future drug resistance.

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OdDHL Inhibits T Cell Subset Differentiation and Delays Diabetes Onset in NOD Mice

Cited by 5 publications

References 30 publications

Role of intestinal microbiota and metabolites on gut homeostasis and human diseases

Role of intestinal microbiota and metabolites on gut homeostasis and human diseases

Amelioration of Autoimmune Diabetes of NOD Mice by Immunomodulating Probiotics

Potential Therapeutic Targets for Combination Antibody Therapy against Pseudomonas aeruginosa Infections

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