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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.)

Caspase-1 but Not Caspase-11 Is Required for NLRC4-Mediated Pyroptosis and Restriction of Infection by Flagellated Legionella Species in Mouse Macrophages and In Vivo

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Cerqueira, Daiane M. [1] ; Pereira, Marcelo S. F. [1] ; Silva, Alexandre L. N. [1] ; Cunha, Larissa D. [1] ; Zamboni, Dario S. [1]
Total Authors: 5
[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Cell Biol, BR-14049900 Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: JOURNAL OF IMMUNOLOGY; v. 195, n. 5, p. 2303-2311, SEP 1 2015.
Web of Science Citations: 32

Gram-negative bacteria from the Legionella genus are intracellular pathogens that cause a severe form of pneumonia called Legionnaires' disease. The bacteria replicate intracellularly in macrophages, and the restriction of bacterial replication by these cells is critical for host resistance. The activation of the NAIP5/NLRC4 inflammasome, which is readily triggered in response to bacterial flagellin, is essential for the restriction of bacterial replication in murine macrophages. Once activated, this inflammasome induces pore formation and pyroptosis and facilitates the restriction of bacterial replication in macrophages. Because investigations related to the NLRC4-mediated restriction of Legionella replication were performed using mice double deficient for caspase-1 and caspase-11, we assessed the participation of caspase-1 and caspase-11 in the functions of the NLRC4 inflammasome and the restriction of Legionella replication in macrophages and in vivo. By using several species of Legionella and mice singly deficient for caspase-1 or caspase-11, we demonstrated that caspase-1 but not caspase-11 was required for pore formation, pyroptosis, and restriction of Legionella replication in macrophages and in vivo. By generating F-1 mice in a mixed 129 x C57BL/6 background deficient (129 x Casp-11(-/-)) or sufficient (129 x C57BL/6) for caspase-11 expression, we found that caspase-11 was dispensable for the restriction of Legionella pneumophila replication in macrophages and in vivo. Thus, although caspase-11 participates in flagellin-independent noncanonical activation of the NLRP3 inflammasome, it is dispensable for the activities of the NLRC4 inflammasome. In contrast, functional caspase-1 is necessary and sufficient to trigger flagellin/NLRC4-mediated restriction of Legionella spp. infection in macrophages and in vivo. (AU)

FAPESP's process: 12/14456-3 - Subversion of inflammasome functions by Coxiella burnetii
Grantee:Larissa Dias da Cunha
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 11/22617-4 - Determination of the functional mechanisms that operate in the signaling pathway flagellin- NLRC4-dependent/caspase1-independent for restriction of L. pneumophila infection and determination of the mechanisms that operate in a flagellin-independent manner
Grantee:Marcelo de Souza Fernandes Pereira
Support Opportunities: Scholarships in Brazil - Post-Doctoral
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: 14/04684-4 - The inflammasome in the host response against intracellular pathogens and the microbial mechanisms for its evasion
Grantee:Dario Simões Zamboni
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 12/15932-3 - The role of NLRC4 and ASC in recognition and control of infection with Leishmania (L.) amazonensis.
Grantee:Alexandre Luiz Neves Silva
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 12/16941-6 - Temporal and transcriptional inflammasomes regulation in Legionella pneumophila recognition by macrophages
Grantee:Daiane Maria Cerqueira
Support Opportunities: Scholarships in Brazil - Master