Gut microbiota translocation to the pancreatic lymph nodes triggers NOD2 activation and contributes to T1D onset

Costa, Frederico R. C.; Francozo, Marcela; Oliveira, Gabriela Gonçalves de; Ignácio, Aline; Castoldi, Ângela; Zamboni, Dario S.; Ramos, Simone G.; Câmara, Niels Olsen Saraiva; Zoete, Marcel R. de; Palm, Noah W.; Flavell, Richard A.; Silva, João; Carlos, Daniela

doi:10.1084/jem.20150744

Cited by 153 publications

(169 citation statements)

References 70 publications

(89 reference statements)

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“…Costa reported recently that Nod2 is important in streptozotocin-induced diabetes in C57BL/6 mice [27]. Although both our study and theirs demonstrated increased Tregs in response to Nod2 -/-microbiota, the cause of the Treg increase in the two model systems was different.…”

Section: Nod2contrasting

confidence: 61%

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Nucleotide-binding oligomerization domain-containing protein 2 (Nod2) modulates T1DM susceptibility by gut microbiota

Pearson

Chen

et al. 2017

Journal of Autoimmunity

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Section: Nod2contrasting

confidence: 61%

“…These results suggest that the Mφ and DCs are not responsible for altered Nod2-mediated spontaneous diabetes susceptibility, unlike the streptozotocin-induced model [27]. (Fig.…”

Section: Effect Of Nod2 On Macrophages (Mφ) and Dendritic Cells (Dcs)mentioning

confidence: 77%

Nucleotide-binding oligomerization domain-containing protein 2 (Nod2) modulates T1DM susceptibility by gut microbiota

Pearson

Chen

et al. 2017

Journal of Autoimmunity

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“…However, if these mechanisms fail, the mesenteric lymph nodes (MLNs) and liver represent further “firewalls” against commensal bacteria that escape the gut (2, 4, 7). Such mechanisms occur only during intestinal or vascular pathology, during chemotherapy, or in the absence of a functional innate immune system (2, 6, 8–11). Although recent studies show that gut commensals can reside within gastrointestinal-associated lymphoid tissues of unmanipulated, healthy hosts, it is unclear whether pathobiont translocation is involved in systemic autoimmunity (12).…”

mentioning

confidence: 99%

Translocation of a gut pathobiont drives autoimmunity in mice and humans

Vieira

Hiltensperger

Kumar

et al. 2018

Science

639

452

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Despite multiple associations between the microbiota and immune diseases, their role in autoimmunity is poorly understood. We found that translocation of a gut pathobiont, Enterococcus gallinarum, to the liver and other systemic tissues triggers autoimmune responses in a genetic background predisposing to autoimmunity. Antibiotic treatment prevented mortality in this model, suppressed growth of E. gallinarum in tissues, and eliminated pathogenic autoantibodies and Tcells. Hepatocyte–E. gallinarum cocultures induced autoimmune-promoting factors. Pathobiont translocation in monocolonized and autoimmune-prone mice induced autoantibodies and caused mortality, which could be prevented by an intramuscular vaccine targeting the pathobiont. E. gallinarum–specific DNA was recovered from liver biopsies of autoimmune patients, and cocultures with human hepatocytes replicated the murine findings; hence, similar processes apparently occur in susceptible humans. These discoveries show that a gut pathobiont can translocate and promote autoimmunity in genetically predisposed hosts.

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“…This early-life treatment reduced the percentage of Treg and Th17 cells in lamina propria (LP), which may have contributed to the accelerated diabetes development. In the Streptozotocin (STZ)-induced type 1 diabetes model, mice treated with antibiotics were fully protected from diabetes (84). This was attributed to blocking pro-diabetic bacteria translocation to PLN (84).…”

Section: Shaping the Immune System Via Alterations In Gut Bacteriamentioning

confidence: 99%

Antibiotics, gut microbiota, environment in early life and type 1 diabetes

Wong

2017

Pharmacological Research

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The gut microbiota interact with innate immune cells and play an important role in shaping the immune system. Many factors may influence the composition of the microbiota such as mode of birth, diet, infections and medication including antibiotics. In diseases with a multifactorial etiology, like type 1 diabetes, manipulation and alterations of the microbiota in animal models has been shown to influence the incidence and onset of disease. The microbiota are an important part of the internal environment and understanding how these bacteria interact with the innate immune cells to generate immune tolerance may open up opportunities for development of new therapeutic strategies. In this review, we discuss recent findings in relation to the microbiota, particularly in the context of type 1 diabetes.

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Gut microbiota translocation to the pancreatic lymph nodes triggers NOD2 activation and contributes to T1D onset

Abstract: Streptozotocin causes T1D by inducing the translocation of intestinal bacteria into pancreatic lymph nodes and driving the development of pathogenic Th1 and Th17 cells through NOD2 receptor.

Cited by 153 publications

References 70 publications

Nucleotide-binding oligomerization domain-containing protein 2 (Nod2) modulates T1DM susceptibility by gut microbiota

Nucleotide-binding oligomerization domain-containing protein 2 (Nod2) modulates T1DM susceptibility by gut microbiota

Translocation of a gut pathobiont drives autoimmunity in mice and humans

Antibiotics, gut microbiota, environment in early life and type 1 diabetes

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