| Full text | |
| Author(s): |
Ketelut-Carneiro, Natalia
[1]
;
Silva, Grace Kelly
[1]
;
Rocha, Fernanda Agostini
[1]
;
Milanezi, Cristiane Maria
[1]
;
Cavalcanti-Neto, Florencio Figueiredo
[2]
;
Zamboni, Dario Simoes
[3]
;
Silva, Joao Santana
[1]
Total Authors: 7
|
| Affiliation: | [1] Univ Sao Paulo, Ribeira Preto Med Sch, Dept Biochem & Immunol, BR-14049900 Sao Paulo - Brazil
[2] Univ Brasilia, Dept Pathol, BR-70910900 Brasilia, DF - Brazil
[3] Univ Sao Paulo, Ribeira Preto Med Sch, Dept Cell Biol, BR-14049900 Sao Paulo - Brazil
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | JOURNAL OF IMMUNOLOGY; v. 194, n. 9, p. 4507-4517, MAY 1 2015. |
| Web of Science Citations: | 31 |
| Abstract | |
Pathogens are sensed by innate immune receptors that initiate an efficient adaptive immune response upon activation. The elements of the innate immune recognition process for Paracoccidioides brasiliensis include TLR-2, TLR-4, and dectin-1. However, there are additional receptors necessary for the host immune responses to P. brasiliensis. The nucleotide-binding oligomerization domain-like receptor (NLRs), which activate inflammasomes, are candidate receptors that deserve renewed investigation. After pathogen infection, the NLRs form large signaling platforms called inflammasomes, which lead to caspase-1 activation and maturation of proinflammatory cytokines (IL-18 and IL-1 beta). In this study, we showed that NLR family pyrin domain-containing 3 (Nlrp3) is required to induce caspase-1 activation and further secretion of IL-1 beta and IL-18 by P. brasiliensis-infected macrophages. Additionally, potassium efflux and lysosomal acidification induced by the fungus were important steps in the caspase-1 activation mechanism. Notably, Nlrp3 and caspase-1 knockout mice were more susceptible to infection than were the wild-type animals, suggesting that the Nlrp3-dependent inflammasomes contribute to host protection against P. brasiliensis. This protective effect occurred owing to the inflammatory response mediated by IL-18, as shown by an augmented fungus burden in IL-18 knockout mice. Taken together, our results show that the Nlrp3 inflammasome is essential for resistance against P. brasiliensis because it orchestrates robust caspase-1 activation and triggers an IL-18-dependent proinflammatory response. (AU) | |
| 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 |
| FAPESP's process: | 13/21295-9 - Role of canonical and non-canonical inflammasome in modulating the innate immune response during infection with Paracoccidioides brasiliensis |
| Grantee: | Natália Ketelut Carneiro |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 12/14524-9 - Modulation of T lymphocytes differentiation in infections by Protozoa, Fungi and Bacteria |
| Grantee: | João Santana da Silva |
| Support Opportunities: | Research Projects - Thematic Grants |