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Browse ATS 2021 Abstracts

HomeProgram ▶ Browse ATS 2021 Abstracts
 

ATS 2021 will feature presentations of original research from accepted abstracts. Mini Symposia and Thematic Poster Sessions are abstract based sessions.

Please use the form below to browse scientific abstracts and case reports accepted for ATS 2021. Abstracts presented at the ATS 2021 will be published in the Online Abstract Issue of the American Journal of Respiratory and Critical Care Medicine, Volume 203, May 3, 2021.

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Inhibition of NLRP3 Inflammasome Reduces the Intracellular Survival of Non-Typeable Haemophilus Influenzae Isolated from Patients with COPD

Session Title
TP105 - TP105 BASIC MECHANISMS OF LUNG INFECTIONS: FROM SARS-COV-2 TO INFLUENZA
Abstract
A4169 - Inhibition of NLRP3 Inflammasome Reduces the Intracellular Survival of Non-Typeable Haemophilus Influenzae Isolated from Patients with COPD
Author Block: Z. Jevnikar Rojnik1, M. Rhedin2, B. Collins2, J. Jirholt2; 1Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, 2Bioscience COPD/IPF, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Introduction: The NLRP3 inflammasome is a critical component of the innate immune system that mediates caspase-1 activation and the secretion of pro-inflammatory cytokines in response to microbial infection and cellular damage. NLRP3 has been shown to enhance bacterial survival by modulating monocyte biology and our aim was to investigate the potential of NLRP3 inhibitors to affect the intracellular survival of Non-typeable Haemophilus influenzae (NTHi), a bacteria frequently associated with exacerbations in COPD patients. Methods: THP-1 human monocytes were infected with NTHi (strain 11P6H) isolated from sputum of patients with COPD and the NLRP3 inflammasome was activated by adenosine triphosphate (ATP). The effect of the selective NLRP3 inflammasome inhibitor MCC950 on pro-inflammatory cytokines production and intracellular bacterial survival was analysed by ELISA/MSD and the gentamicin protection assay, respectively. Results: ATP activation induced a robust NLRP3-specific pro-inflammatory response in THP-1 monocytes infected with NTHi compared to non-infected cells. MCC950 efficiently blocked IL-18 and active IL-1β production and reduced ATP-driven intracellular survival of NTHi in THP-1 monocytes. Conclusions: Pharmacological inhibition of NLRP3 inflammasome activation in human monocytes dampens a pro-inflammatory response and reduces the survival of NTHi, the key bacterial pathogen associated with COPD pathology. This provides a rational to target NLRP3 inflammasome activation in COPD patients with chronic NTHi infection in the lungs.