ASC and NLRP3 impair host defense during lethal pneumonia caused by serotype 3 Streptococcus pneumoniae in mice
| Autor: | Onno J. de Boer, Sanne Terpstra, Tom van der Poll, Sandrine Florquin, Mark C. Dessing, Alex F. de Vos, Regina de Beer, Alexander P. N. A. de Porto, Miriam H. P. van Lieshout, Cornelis van 't Veer |
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| Přispěvatelé: | APH - Mental Health, AII - Infectious diseases, Center of Experimental and Molecular Medicine, AII - Amsterdam institute for Infection and Immunity, Pathology, Graduate School, ACS - Amsterdam Cardiovascular Sciences, Infectious diseases, ACS - Pulmonary hypertension & thrombosis, ACS - Heart failure & arrhythmias |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Serotype Immunology Biology medicine.disease_cause Pyrin domain Microbiology Mice 03 medical and health sciences Immune system NLR Family Pyrin Domain-Containing 3 Protein Streptococcus pneumoniae medicine Animals Immunology and Allergy Receptor Mice Knockout Streptococcus Caspase 1 Inflammasome Pneumonia Pneumococcal medicine.disease Immunity Innate Toll-Like Receptor 2 CARD Signaling Adaptor Proteins Community-Acquired Infections Mice Inbred C57BL Toll-Like Receptor 4 Pneumonia 030104 developmental biology Myeloid Differentiation Factor 88 Signal Transduction medicine.drug |
| Zdroj: | European Journal of Immunology, 48(1), 66-79. Wiley-VCH Verlag European journal of immunology, 48(1), 66-79. Wiley-VCH Verlag |
| ISSN: | 0014-2980 |
| DOI: | 10.1002/eji.201646554 |
| Popis: | Streptococcus (S.) pneumoniae is the most common cause of community-acquired pneumonia. The Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, consisting of NLRP3, ASC (the adaptor apoptosis-associated speck-like protein containing a CARD) and caspase-1, has been implicated in protective immunity during pneumonia induced by high doses of S. pneumoniae serotype 2. Here we investigated the role of the NLRP3 inflammasome in the host response during lethal airway infection with a low dose of serotype 3 S. pneumoniae. Mice were euthanized at predefined endpoints for analysis or observed in survival studies. In additional studies, Tlr2(-/-)/Tlr4(-/-) mice and Myd88(-/-) mice incapable of Toll-like receptor signaling were studied. In stark contrast with existing literature, both Nlrp3(-/-) and Asc(-/-) mice showed a strongly improved host defense, as reflected by a markedly reduced mortality rate accompanied by diminished bacterial growth and dissemination. Host defense was unaltered in Tlr2(-/-)/Tlr4(-/-) mice and Myd88(-/-) mice. These results show that the NLRP3 inflammasome impairs host defense during lethal pneumonia caused by serotype 3 S. pneumoniae. Our findings challenge the current paradigm that proximal innate detection systems are indispensable for an adequate host immune response against bacteria |
| Databáze: | OpenAIRE |
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