A Novel Norepinephrine-β2-Adrenoceptor Based Therapy for Pseudomonas aeruginosa Keratitis Via Regulating Bacterial Virulence and Inflammatory Response

2019 ◽  
Author(s):  
Xiubin Ma ◽  
Qun Wang ◽  
Fangying Song ◽  
Ya Li ◽  
Jing Li ◽  
...  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adriana Valeria Jäger ◽  
Paula Arias ◽  
Maria Virginia Tribulatti ◽  
Marcela Adriana Brocco ◽  
Maria Victoria Pepe ◽  
...  

AbstractPathogens phagocytosis and the uptake of apoptotic cells (efferocytosis) are essential macrophages tasks, classically considered as mutually exclusive. Macrophages have been observed to polarize into either pro-inflammatory/microbicidal or anti-inflammatory/efferocytic phenotypes. However, macrophage functions have shown to be more complex. Furthermore, little is known about the regulation of efferocytosis under inflammatory conditions. In this study, we elucidate the modulation of the macrophage efferocytic function during an inflammatory stimulus. We find that bone marrow-derived macrophages (BMDM) are very efficient in engulfing both the bacterial pathogen Pseudomonas aeruginosa and apoptotic cells. BMDM showed a high bactericidal capacity unaffected by the concomitant presence of apoptotic material. Plasticity in macrophage programming, in response to changing environmental cues, may modulate efferocytic capability. In this work, we further show that, after phagocyting and processing Pseudomonas aeruginosa, macrophages highly increase their efferocytic capacity without affecting their phagocytic function. Moreover, we demonstrate that Pseudomonas aeruginosa enhances efferocytosis of these phagocytes through the IL-6 signaling pathway. Our results show that the inflammatory response generated by the bacterial processing enhances these macrophages’ capacity to control inflammation through an increased efferocytosis.


Virulence ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 1163-1175 ◽  
Author(s):  
Magali Garcia ◽  
Eric Morello ◽  
Julien Garnier ◽  
Christine Barrault ◽  
Martine Garnier ◽  
...  

2018 ◽  
Vol 314 (4) ◽  
pp. L635-L641 ◽  
Author(s):  
Manon Ruffin ◽  
Lucie Roussel ◽  
Émilie Maillé ◽  
Simon Rousseau ◽  
Emmanuelle Brochiero

Cystic fibrosis patients exhibit chronic Pseudomonas aeruginosa respiratory infections and sustained proinflammatory state favoring lung tissue damage and remodeling, ultimately leading to respiratory failure. Loss of cystic fibrosis transmembrane conductance regulator (CFTR) function is associated with MAPK hyperactivation and increased cytokines expression, such as interleukin-8 [chemoattractant chemokine (C-X-C motif) ligand 8 (CXCL8)]. Recently, new therapeutic strategies directly targeting the basic CFTR defect have been developed, and ORKAMBI (Vx-809/Vx-770 combination) is the only Food and Drug Administration-approved treatment for CF patients homozygous for the F508del mutation. Here we aimed to determine the effect of the Vx-809/Vx-770 combination on the induction of the inflammatory response by fully differentiated primary bronchial epithelial cell cultures from CF patients carrying F508del mutations, following exposure to P. aeruginosa exoproducts. Our data unveiled that CFTR functional rescue with Vx-809/Vx-770 drastically reduces CXCL8 (as well as CXCL1 and CXCL2) transcripts and p38 MAPK phosphorylation in response to P. aeruginosa exposure through a CFTR-dependent mechanism. These results suggest that ORKAMBI has anti-inflammatory properties that could decrease lung inflammation and contribute to the observed beneficial impact of this treatment in CF patients.


2019 ◽  
Vol 10 (9) ◽  
pp. 5759-5767
Author(s):  
Wan-Ting Lee ◽  
Boon-Khai Tan ◽  
Su-Anne Eng ◽  
Gan Chee Yuen ◽  
Kit Lam Chan ◽  
...  

A strategy to circumvent the problem of multidrug resistant pathogens is the discovery of anti-infectives targeting bacterial virulence or host immunity.


2019 ◽  
Vol 111 (5) ◽  
pp. 1195-1210 ◽  
Author(s):  
Yaqin Song ◽  
Chun Yang ◽  
Gukui Chen ◽  
Yixi Zhang ◽  
Zijing Seng ◽  
...  

2011 ◽  
Vol 78 (2) ◽  
pp. 593-595 ◽  
Author(s):  
Marion Le Coadic ◽  
Marianne Simon ◽  
Anna Marchetti ◽  
Dieter Ebert ◽  
Pierre Cosson

ABSTRACTWe show thatDaphnia magnacan be used to assess acute virulence of pathogens relevant to human health, such asPseudomonas aeruginosaorPhotorhabdus asymbiotica. Analysis of bacterial mutants suggests thatP. aeruginosauses similar mechanisms to infectDaphniaand other hosts.


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