| Literature DB >> 28971472 |
Miriam H P van Lieshout1,2, Alex F de Vos1,2, Mark C Dessing3, Alexander P N A de Porto1,2, Onno J de Boer3, Regina de Beer1,2, Sanne Terpstra1,2, Sandrine Florquin3, Cornelis Van't Veer1,2, Tom van der Poll1,2,4.
Abstract
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.Entities:
Keywords: Bacterial infection; Inflammasome; MyD88; Pneumonia; Toll-like receptors
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Year: 2017 PMID： 28971472 DOI： 10.1002/eji.201646554
Source DB: PubMed Journal: Eur J Immunol ISSN： 0014-2980 Impact factor: 5.532