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Title: | NLRP3 and ASC differentially affect the lung transcriptome during pneumococcal pneumonia |
Authors: | Lieshout, Miriam H. van Scicluna, Brendon P. Florquin, Sandrine Poll, Tom van der |
Keywords: | Pulmonary artery -- Diseases Inflammation -- Immunological aspects Drug receptors -- Research Cytoskeletal proteins Host-parasite relationships -- Genetic aspects |
Issue Date: | 2014 |
Publisher: | American Thoracic Society |
Citation: | van Lieshout, M. H., Scicluna, B. P., Florquin, S., & van der Poll, T. (2014). NLRP3 and ASC differentially affect the lung transcriptome during pneumococcal pneumonia. American Journal of Respiratory Cell and Molecular Biology, 50(4), 699-712. |
Abstract: | Streptococcus pneumoniae is the most frequently isolated causative pathogen of community-acquired pneumonia, a leading cause of mortality worldwide. Inflammasomes are multiprotein complexes that play crucial roles in the regulation of inflammation. Nod-like receptor family, pyrin domain containing (NLRP) 3 is a sensor that functions in a single inflammasome, whereas adaptor apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) is a common adaptor of several inflammasomes. We investigated the role of NLRP3 and ASC during S. pneumoniae pneumonia by comparing bacterial growth and spreading, and host innate immune responses in wild-type mice and mice deficient for either NLRP3 (Nlrp3(-/-)) or ASC (Asc(-/-)). Asc(-/-) mice had increased bacterial dissemination and lethality compared with Nlrp3(-/-) mice, although the cytokine response was impaired in both mouse strains. By detailed analysis of the early inflammatory response in the lung by whole-genome transcriptional profiling, we identified several mediators that were differentially expressed between Nlrp3(-/-) and Asc(-/-) mice. Of these, IL-17, granulocyte/macrophage colony-stimulating factor, and integrin-αM were significantly attenuated in Asc(-/-) relative to Nlrp3(-/-) mice, as well as a number of genes involved in the adaptive immune response. These differences may explain the increased susceptibility of Asc(-/ -) mice during S. pneumoniae infection, and suggest that either ASC-dependent NLRP3-independent inflammasomes or inflammasome-independent ASC functions may be involved. |
URI: | https://www.um.edu.mt/library/oar/handle/123456789/98001 |
Appears in Collections: | Scholarly Works - FacHScABS |
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NLRP3_and_ASC_differentially_affect_the_lung_transcriptome_during_pneumococcal_pneumonia.pdf Restricted Access | 1.96 MB | Adobe PDF | View/Open Request a copy |
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