| Full text | |
| Author(s): |
Ketelut-Carneiro, Natalia
[1]
;
Ghosh, Sreya
[2]
;
Levitz, Stuart M.
[2]
;
Fitzgerald, Katherine A.
[2]
;
da Silva, Joao Santana
[1]
Total Authors: 5
|
| Affiliation: | [1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Ribeirao Preto, SP - Brazil
[2] Univ Massachusetts, Sch Med, Dept Med, Program Innate Immun, Worcester, MA - USA
Total Affiliations: 2
|
| Document type: | Journal article |
| Source: | Journal of Infectious Diseases; v. 217, n. 2, p. 329-339, JAN 15 2017. |
| Web of Science Citations: | 4 |
| Abstract | |
Background. Paracoccidioides brasiliensis is equipped with an arsenal of virulence factors that are crucial for causing infection. Our group previously defined the NLRP3 inflammasome as a mediator of P brasiliensis-induced cell damage recognition and induction of effective Th1 immune responses. However, deficiency of caspase-1 only partially reduced interleukin (IL)-1 ss levels. Methods. In this study, using chemical inhibitors as well as genetically modified mice, we identify an additional pathway for IL-1 ss production in response to P brasiliensis infection. Results. Paracoccidioides brasiliensis initiated caspase-8-mediated IL-1 ss production, an event that was necessary for transcriptional priming and posttranslational processing of pro-IL-1 ss. Caspase-8 synergizes with the canonical NLRP3 inflammasome pathway to control caspase-1 processing and IL-1 ss maturation, providing a regulatory role for caspase-8 in host resistance to in vivo P brasiliensis infection. Conclusions. Taken together, these findings revealed an important role for caspase-8 in the innate immune response of host cells to P brasiliensis infection, demonstrating a connected network between noncanonical and canonical inflammasomes to coordinate IL-1 ss production during fungal challenge. (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 |
| FAPESP's process: | 14/24503-4 - Caspase-8 involvement in mediating efficient canonical NLRP3 inflammasome activation during infection with fungal pathogen |
| Grantee: | Natália Ketelut Carneiro |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate (Direct) |