Inhibition of inflammasome activation by a clinical strain of Klebsiella pneumoniae impairs efferocytosis and leads to bacterial dissemination
| Autor: | Ana Campos Codo, Leonardo L. Santos, Marina F. Visconde, Ana Cristina Gales, Dario S. Zamboni, Amanda Correia Saraiva, Alexandra Ivo de Medeiros |
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| Přispěvatelé: | Universidade Estadual Paulista (Unesp), Universidade de São Paulo (USP), Universidade Federal de São Paulo (UNIFESP) |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MACRÓFAGOS Cancer Research Programmed cell death Inflammasomes Neutrophils Klebsiella pneumoniae Immunology Gene Expression Bacteremia Monocytes Article Microbiology Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Phagocytosis In vivo Pyroptosis medicine Animals Humans lcsh:QH573-671 Efferocytosis Mice Knockout Strain (chemistry) biology lcsh:Cytology Macrophages Caspase 1 Inflammasome Cell Biology biology.organism_classification Caspases Initiator In vitro Interleukin-10 Klebsiella Infections Mice Inbred C57BL 030104 developmental biology Caspases Host-Pathogen Interactions Female Bacteria 030215 immunology medicine.drug |
| Zdroj: | Cell Death and Disease, Vol 9, Iss 12, Pp 1-14 (2018) Cell Death & Disease Web of Science Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 2041-4889 |
| Popis: | Made available in DSpace on 2019-10-04T12:33:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-12-05 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Klebsiella pneumoniae is a Gram-negative bacterium responsible for severe cases of nosocomial pneumonia. During the infectious process, both neutrophils and monocytes migrate to the site of infection, where they carry out their effector functions and can be affected by different patterns of cell death. Our data show that clinical strains of K. pneumoniae have dissimilar mechanisms for surviving within macrophages; these mechanisms include modulation of microbicidal mediators and cell death. The A28006 strain induced high IL-1 beta production and pyroptotic cell death in macrophages; by contrast, the A54970 strain induced high IL-10 production and low IL-1 beta production by macrophages. Pyroptotic cell death induced by the A28006 strain leads to a significant increase in bacterial sensitivity to hydrogen peroxide, and efferocytosis of the pyroptotic cells results in efficient bacterial clearance both in vitro and in vivo. In addition, the A54970 strain was able to inhibit inflammasome activation and pyroptotic cell death by inducing IL-10 production. Here, for the first time, we present a K. pneumoniae strain able to inhibit inflammasome activation, leading to bacterial survival and dissemination in the host. The understanding of possible escape mechanisms is essential in the search for alternative treatments against multidrug-resistant bacteria. Sao Paulo State Univ, Sch Pharmaceut Sci, Dept Biol Sci, Araraquara, SP, Brazil Univ Sao Paulo, Sch Med, Dept Cell & Mol Biol & Pathogen Bioagents, Ribeirao Preto, SP, Brazil Univ Fed Sao Paulo, Dept Internal Med, Escola Paulista Med, Div Infect Dis, Sao Paulo, SP, Brazil Sao Paulo State Univ, Sch Pharmaceut Sci, Dept Biol Sci, Araraquara, SP, Brazil FAPESP: 2011/17611-7 FAPESP: 2013/18039-0 FAPESP: 2017/19870-6 FAPESP: 2017/19265-5 CNPq: 302097/2010-4 CNPq: 471945/2012-9 CNPq: 305535/2014-5 CNPq: 116820/2016-0 CNPq: 159637/2017-1 : PROPG/UNESP - 05/2018 |
| Databáze: | OpenAIRE |
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