Type

Journal Article

Authors

Noel G McElvaney
Emer P Reeves
Vijay K Kuchroo
Mitsuomi Hirashima
Kerstin Pohl
Nessa Banville
Cormac McCarthy
Oliver J McElvaney
David A Bergin
Isabel Vega-Carrascal

Subjects

Microbiology

Topics
pseudomonas aeruginosa humans lgals9 protein human cystic fibrosis havcr2 protein human lipopolysaccharides female immunology membrane proteins galectins microbiology neutrophils signal transduction male pathology lung

Galectin-9 signaling through TIM-3 is involved in neutrophil-mediated Gram-negative bacterial killing: an effect abrogated within the cystic fibrosis lung. (2014)

Abstract The T cell Ig and mucin domain-containing molecule (TIM) family of receptors have emerged as potential therapeutic targets to correct abnormal immune function in chronic inflammatory conditions. TIM-3 serves as a functional receptor in structural cells of the airways and via the ligand galectin-9 (Gal-9) can modulate the inflammatory response. The aim of this study was to investigate TIM-3 expression and function in neutrophils, focusing on its potential role in cystic fibrosis (CF) lung disease. Results revealed that TIM-3 mRNA and protein expression values of circulating neutrophils were equal between healthy controls (n = 20) and people with CF (n = 26). TIM-3 was detected on resting neutrophil membranes by FACS analysis, and expression levels significantly increased post IL-8 or TNF-α exposure (p < 0.05). Our data suggest a novel role for TIM-3/Gal-9 signaling involving modulation of cytosolic calcium levels. Via TIM-3 interaction, Gal-9 induced neutrophil degranulation and primed the cell for enhanced NADPH oxidase activity. Killing of Pseudomonas aeruginosa was significantly increased upon bacterial opsonization with Gal-9 (p < 0.05), an effect abrogated by blockade of TIM-3 receptors. This mechanism appeared to be Gram-negative bacteria specific and mediated via Gal-9/ LPS binding. Additionally, we have demonstrated that neutrophil TIM-3/Gal-9 signaling is perturbed in the CF airways due to proteolytic degradation of the receptor. In conclusion, results suggest a novel neutrophil defect potentially contributing to the defective bacterial clearance observed in the CF airways and suggest that manipulation of the TIM-3 signaling pathway may be of therapeutic value in CF, preferably in conjunction with antiprotease treatment.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Noel G McElvaney, Emer P Reeves, Vijay K Kuchroo, Mitsuomi Hirashima, Kerstin Pohl, Nessa Banville, Cormac McCarthy, Oliver J McElvaney, David A Bergin, Isabel Vega-Carrascal

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Emer P Reeves
Royal College of Surgeons in Ireland
Total Publications: 63
 
3
Kerstin Pohl
Royal College of Surgeons in Ireland
 
4
Nessa Banville
Maynooth University
Total Publications: 9
 
5
Cormac McCarthy
Royal College of Surgeons in Ireland
Total Publications: 19
 
6
Oliver J McElvaney
Royal College of Surgeons in Ireland
 
7
David A Bergin
Royal College of Surgeons in Ireland
Total Publications: 28