scholarly journals Pseudomonas aeruginosa infection reveals a Caspase-1-dependent neutrophil pyroptosis pathway that restrains damaging Histone release

2021 ◽  
Author(s):  
Remi Planes ◽  
Karin Santoni ◽  
Salimata Bagayoko ◽  
David Pericat ◽  
Pierre-Jean Bordignon ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Mouse Models ◽  
Regulatory Function ◽  
Cytokine Release ◽  
Caspase 1 ◽  
Pseudomonas Aeruginosa Infection

Neutrophils mediate essential immune and microbicidal processes. Consequently, to counteract neutrophil attack, pathogens have developed various virulence strategies. Here, we showed that Pseudomonas aeruginosa (P. aeruginosa) phospholipase ExoU drives pathological NETosis in neutrophils. Surprisingly, inhibition of ExoU activity uncovered a fully functional Caspase-1-driven pyroptosis pathway in neutrophils. Mechanistically, activated NLRC4 inflammasome promoted Caspase-1-dependent Gasdermin-D activation, IL-1β cytokine release and neutrophil pyroptosis. Whereas both pyroptotic and netotic neutrophils released alarmins, only NETosis liberated the destructive DAMPs Histones, which exacerbated Pseudomonas-induced mouse lethality. To the contrary, subcortical actin allowed pyroptotic neutrophils to physically limit poisonous inflammation by keeping Histones intracellularly. Finally, mouse models of infection highlighted that both NETosis and neutrophil Caspase-1 contributed to P. aeruginosa spreading. Overall, we established the host deleterious consequences of Pseudomonas-induced-NETosis but also uncovered an unsuspected ability of neutrophils to undergo Caspase-1-dependent pyroptosis, a process where neutrophils exhibit a self-regulatory function that limit Histone release.

scholarly journals cAMP signaling primes lung endothelial cells to activate caspase-1 during Pseudomonas aeruginosa infection

2020 ◽  
Vol 318 (5) ◽  
pp. L1074-L1083 ◽  
Author(s):  
Phoibe Renema ◽  
Kierra S. Hardy ◽  
Nicole Housley ◽  
Grace Dunbar ◽  
Naga Annamdevula ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Endothelial Cells ◽  
De Novo ◽  
Camp Signaling ◽  
Partial Explanation ◽  
Caspase 1 ◽  
Cell Flow Cytometry ◽  
Pseudomonas Aeruginosa Infection ◽  
Lung Endothelial Cells ◽  
Camp Levels

Activation of the inflammasome-caspase-1 axis in lung endothelial cells is emerging as a novel arm of the innate immune response to pneumonia and sepsis caused by Pseudomonas aeruginosa. Increased levels of circulating autacoids are hallmarks of pneumonia and sepsis and induce physiological responses via cAMP signaling in targeted cells. However, it is unknown whether cAMP affects other functions, such as P. aeruginosa-induced caspase-1 activation. Herein, we describe the effects of cAMP signaling on caspase-1 activation using a single cell flow cytometry-based assay. P. aeruginosa infection of cultured lung endothelial cells caused caspase-1 activation in a distinct population of cells. Unexpectedly, pharmacological cAMP elevation increased the total number of lung endothelial cells with activated caspase-1. Interestingly, addition of cAMP agonists augmented P. aeruginosa infection of lung endothelial cells as a partial explanation underlying cAMP priming of caspase-1 activation. The cAMP effect(s) appeared to function as a priming signal because addition of cAMP agonists was required either before or early during the onset of infection. However, absolute cAMP levels measured by ELISA were not predictive of cAMP-priming effects. Importantly, inhibition of de novo cAMP synthesis decreased the number of lung endothelial cells with activated caspase-1 during infection. Collectively, our data suggest that lung endothelial cells rely on cAMP signaling to prime caspase-1 activation during P. aeruginosa infection.

scholarly journals Caspase-1 Cleavage of the TLR Adaptor TRIF Inhibits Autophagy and β-Interferon Production during Pseudomonas aeruginosa Infection

2014 ◽  
Vol 15 (2) ◽  
pp. 214-227 ◽  
Author(s):  
Majid Sakhi Jabir ◽  
Neil D. Ritchie ◽  
Dong Li ◽  
Hannah K. Bayes ◽  
Panagiotis Tourlomousis ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Interferon Production ◽  
Caspase 1 ◽  
Pseudomonas Aeruginosa Infection

The effect of the antiinflammatory IL-1R antagonist anakinra in mice with CF-like lung disease and Pseudomonas aeruginosa infection

Pneumologie ◽  
2016 ◽  
Vol 70 (07) ◽  
Author(s):  
A Schütte ◽  
Z Zhou-Suckow ◽  
J Schatterny ◽  
S Schmidt ◽  
S Hassel ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Lung Disease ◽  
Pseudomonas Aeruginosa Infection

scholarly journals Epidemiology of first/new Pseudomonas aeruginosa infection in cystic fibrosis patients

2010 ◽  
Vol 9 ◽  
pp. S29 ◽  
Author(s):  
L. Zavataro ◽  
G. Taccetti ◽  
L. Cariani ◽  
N. Ravenni ◽  
G. Braccini ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Pseudomonas Aeruginosa Infection

scholarly journals Rapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rachel Wheatley ◽  
Julio Diaz Caballero ◽  
Natalia Kapel ◽  
Fien H. R. de Winter ◽  
Pramod Jangir ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Efflux Pump ◽  
Rapid Evolution ◽  
Carbapenem Resistance ◽  
Host Immunity ◽  
High Definition ◽  
Loss Of Resistance ◽  
Pseudomonas Aeruginosa Infection ◽  
Second Wave

AbstractIt is well established that antibiotic treatment selects for resistance, but the dynamics of this process during infections are poorly understood. Here we map the responses of Pseudomonas aeruginosa to treatment in high definition during a lung infection of a single ICU patient. Host immunity and antibiotic therapy with meropenem suppressed P. aeruginosa, but a second wave of infection emerged due to the growth of oprD and wbpM meropenem resistant mutants that evolved in situ. Selection then led to a loss of resistance by decreasing the prevalence of low fitness oprD mutants, increasing the frequency of high fitness mutants lacking the MexAB-OprM efflux pump, and decreasing the copy number of a multidrug resistance plasmid. Ultimately, host immunity suppressed wbpM mutants with high meropenem resistance and fitness. Our study highlights how natural selection and host immunity interact to drive both the rapid rise, and fall, of resistance during infection.

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