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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

A Dectin-1-Caspase-8 Pathway Licenses Canonical Caspase-1 Inflammasome Activation and Interleukin-1 beta Release in Response to a Pathogenic Fungus

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Ketelut-Carneiro, Natalia [1] ; Ghosh, Sreya [2] ; Levitz, Stuart M. [2] ; Fitzgerald, Katherine A. [2] ; da Silva, Joao Santana [1]
Total Authors: 5
[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

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: 13/21295-9 - Role of canonical and non-canonical inflammasome in modulating the innate immune response during infection with Paracoccidioides brasiliensis
Grantee:Natália Ketelut Carneiro
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
Grantee:Fernando de Queiroz Cunha
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
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 type: Scholarships abroad - Research Internship - 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 type: Research Projects - Thematic Grants