| Full text | |
| Author(s): Show less - |
Leite, Jefferson Antonio
[1, 2]
;
Pessenda, Gabriela
[1]
;
Guerra-Gomes, Isabel C.
[1]
;
Mendonca de Santana, Alynne Karen
[1]
;
Pereira, Camila Andre
[3]
;
Campos Costa, Frederico Ribeiro
[1]
;
Ramos, Simone G.
[4]
;
Zamboni, Dario Simoes
[5]
;
Caetano Faria, Ana Maria
[6]
;
de Almeida, Danilo Candido
[7]
;
Saraiva Camara, Niels Olsen
[1, 2, 7]
;
Tostes, Rita C.
[3]
;
Silva, Joao Santana
[8]
;
Carlos, Daniela
[1]
Total Authors: 14
|
| Affiliation: | [1] Ribeirao Preto Med Sch, Dept Biochem & Immunol, USP Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Inst Biomed Sci 4, BR-14049900 Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Dept Pharmacol, Ribeirao Preto Med Sch, BR-14049900 Ribeirao Preto, SP - Brazil
[4] Univ Sao Paulo, Dept Pathol & Legal Med, Ribeirao Preto Med Sch, BR-14049900 Ribeirao Preto, SP - Brazil
[5] Univ Sao Paulo, Dept Mol & Cell Biol, Ribeirao Preto Med Sch, BR-14049900 Ribeirao Preto, SP - Brazil
[6] Fed Univ Minas Gerais UFMG, Dept Biochem & Immunol, Inst Biol Sci, BR-31270901 Belo Horizonte, MG - Brazil
[7] Fed Univ Sao Paulo UNIFESP, Dept Immunol, BR-04021001 Sao Paulo, SP - Brazil
[8] Fiocruz Bi Inst Translat Med Platform, BR-14049900 Ribeirao Preto, SP - Brazil
Total Affiliations: 8
|
| Document type: | Journal article |
| Source: | CELLS; v. 9, n. 4 APR 2020. |
| Web of Science Citations: | 0 |
| Abstract | |
Pattern recognition receptors (PRRs), such as Nod2, Nlrp3, Tlr2, Trl4, and Tlr9, are directly involved in type 1 diabetes (T1D) susceptibility. However, the role of the cytosolic DNA sensor, AIM2, in T1D pathogenesis is still unknown. Here, we demonstrate that C57BL/6 mice lacking AIM2 (AIM2(-/-)) are prone to streptozotocin (STZ)-induced T1D, compared to WT C57BL/6 mice. The AIM2(-/-) mice phenotype is associated with a greater proinflammatory response in pancreatic tissues, alterations in gut microbiota and bacterial translocation to pancreatic lymph nodes (PLNs). These alterations are related to an increased intestinal permeability mediated by tight-junction disruption. Notably, AIM2(-/-) mice treated with broad-spectrum antibiotics (ABX) are protected from STZ-induced T1D and display a lower pancreatic proinflammatory response. Mechanistically, the AIM2 inflammasome is activated in vivo, leading to an IL-18 release in the ileum at 15 days after an STZ injection. IL-18 favors RegIII gamma production, thus mitigating gut microbiota alterations and reinforcing the intestinal barrier function. Together, our findings show a regulatory role of AIM2, mediated by IL-18, in shaping gut microbiota and reducing bacterial translocation and proinflammatory response against insulin-producing beta cells, which ultimately results in protection against T1D onset in an STZ-induced diabetes model. (AU) | |
| FAPESP's process: | 12/10395-0 - ROLE OF NLRs RECEPTORS IN IMMUNOREGULATION MECHANISMS OF THE TYPE 1 AND 2 DIABETES: IDENTIFICATION OF POTENTIAL THERAPEUTIC TARGETS |
| Grantee: | Daniela Carlos Sartori |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 16/25116-0 - Evaluation of the expression profile and function of AIM2 inflammasome in intestinal mucosa during diabetes type 1 experimental |
| Grantee: | Jefferson Antonio Leite |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 13/08216-2 - CRID - Center for research in inflammatory diseases. |
| Grantee: | Fernando de Queiroz Cunha |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |