IL-17A impairs host tolerance during airway chronic infection by Pseudomonas aeruginosa

Nicola Ivan Lorè, Cristina Cigana, Camilla Riva, Ida De Fino, Alessandro Nonis, Lorenza Spagnuolo, Barbara Sipione, Lisa Cariani, Daniela Girelli, Giacomo Rossi, Veronica Basso, Carla Colombo, Anna Mondino, Alessandra Bragonzi

Research output: Contribution to journalArticle

Abstract

Resistance and tolerance mechanisms participate to the interplay between host and pathogens. IL-17-mediated response has been shown to be crucial for host resistance to respiratory infections, whereas its role in host tolerance during chronic airway colonization is still unclear. Here, we investigated whether IL-17-mediated response modulates mechanisms of host tolerance during airways chronic infection by P. aeruginosa. First, we found that IL-17A levels were sustained in mice at both early and advanced stages of P. aeruginosa chronic infection and confirmed these observations in human respiratory samples from cystic fibrosis patients infected by P. aeruginosa. Using IL-17a a'/a' or IL-17ra a'/a' mice, we found that the deficiency of IL-17A/IL-17RA axis was associated with: i) increased incidence of chronic infection and bacterial burden, indicating its role in the host resistance to P. aeruginosa; ii) reduced cytokine levels (KC), tissue innate immune cells and markers of tissue damage (pro-MMP-9, elastin degradation, TGF-β 1), proving alteration of host tolerance. Blockade of IL-17A activity by a monoclonal antibody, started when chronic infection is established, did not alter host resistance but increased tolerance. In conclusion, this study identifies IL-17-mediated response as a negative regulator of host tolerance during P. aeruginosa chronic airway infection.

Original languageEnglish
Article number25937
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - May 18 2016

Fingerprint

Interleukin-17
Pseudomonas aeruginosa
Infection
Elastin
Matrix Metalloproteinases
Bacterial Infections
Cystic Fibrosis
Respiratory Tract Infections
Biomarkers
Monoclonal Antibodies
Cytokines
Incidence

ASJC Scopus subject areas

  • General

Cite this

IL-17A impairs host tolerance during airway chronic infection by Pseudomonas aeruginosa. / Lorè, Nicola Ivan; Cigana, Cristina; Riva, Camilla; De Fino, Ida; Nonis, Alessandro; Spagnuolo, Lorenza; Sipione, Barbara; Cariani, Lisa; Girelli, Daniela; Rossi, Giacomo; Basso, Veronica; Colombo, Carla; Mondino, Anna; Bragonzi, Alessandra.

In: Scientific Reports, Vol. 6, 25937, 18.05.2016.

Research output: Contribution to journalArticle

Lorè, Nicola Ivan ; Cigana, Cristina ; Riva, Camilla ; De Fino, Ida ; Nonis, Alessandro ; Spagnuolo, Lorenza ; Sipione, Barbara ; Cariani, Lisa ; Girelli, Daniela ; Rossi, Giacomo ; Basso, Veronica ; Colombo, Carla ; Mondino, Anna ; Bragonzi, Alessandra. / IL-17A impairs host tolerance during airway chronic infection by Pseudomonas aeruginosa. In: Scientific Reports. 2016 ; Vol. 6.
@article{475f6401cee948339eae4c57f942fb1d,
title = "IL-17A impairs host tolerance during airway chronic infection by Pseudomonas aeruginosa",
abstract = "Resistance and tolerance mechanisms participate to the interplay between host and pathogens. IL-17-mediated response has been shown to be crucial for host resistance to respiratory infections, whereas its role in host tolerance during chronic airway colonization is still unclear. Here, we investigated whether IL-17-mediated response modulates mechanisms of host tolerance during airways chronic infection by P. aeruginosa. First, we found that IL-17A levels were sustained in mice at both early and advanced stages of P. aeruginosa chronic infection and confirmed these observations in human respiratory samples from cystic fibrosis patients infected by P. aeruginosa. Using IL-17a a'/a' or IL-17ra a'/a' mice, we found that the deficiency of IL-17A/IL-17RA axis was associated with: i) increased incidence of chronic infection and bacterial burden, indicating its role in the host resistance to P. aeruginosa; ii) reduced cytokine levels (KC), tissue innate immune cells and markers of tissue damage (pro-MMP-9, elastin degradation, TGF-β 1), proving alteration of host tolerance. Blockade of IL-17A activity by a monoclonal antibody, started when chronic infection is established, did not alter host resistance but increased tolerance. In conclusion, this study identifies IL-17-mediated response as a negative regulator of host tolerance during P. aeruginosa chronic airway infection.",
author = "Lor{\`e}, {Nicola Ivan} and Cristina Cigana and Camilla Riva and {De Fino}, Ida and Alessandro Nonis and Lorenza Spagnuolo and Barbara Sipione and Lisa Cariani and Daniela Girelli and Giacomo Rossi and Veronica Basso and Carla Colombo and Anna Mondino and Alessandra Bragonzi",
year = "2016",
month = "5",
day = "18",
doi = "10.1038/srep25937",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - IL-17A impairs host tolerance during airway chronic infection by Pseudomonas aeruginosa

AU - Lorè, Nicola Ivan

AU - Cigana, Cristina

AU - Riva, Camilla

AU - De Fino, Ida

AU - Nonis, Alessandro

AU - Spagnuolo, Lorenza

AU - Sipione, Barbara

AU - Cariani, Lisa

AU - Girelli, Daniela

AU - Rossi, Giacomo

AU - Basso, Veronica

AU - Colombo, Carla

AU - Mondino, Anna

AU - Bragonzi, Alessandra

PY - 2016/5/18

Y1 - 2016/5/18

N2 - Resistance and tolerance mechanisms participate to the interplay between host and pathogens. IL-17-mediated response has been shown to be crucial for host resistance to respiratory infections, whereas its role in host tolerance during chronic airway colonization is still unclear. Here, we investigated whether IL-17-mediated response modulates mechanisms of host tolerance during airways chronic infection by P. aeruginosa. First, we found that IL-17A levels were sustained in mice at both early and advanced stages of P. aeruginosa chronic infection and confirmed these observations in human respiratory samples from cystic fibrosis patients infected by P. aeruginosa. Using IL-17a a'/a' or IL-17ra a'/a' mice, we found that the deficiency of IL-17A/IL-17RA axis was associated with: i) increased incidence of chronic infection and bacterial burden, indicating its role in the host resistance to P. aeruginosa; ii) reduced cytokine levels (KC), tissue innate immune cells and markers of tissue damage (pro-MMP-9, elastin degradation, TGF-β 1), proving alteration of host tolerance. Blockade of IL-17A activity by a monoclonal antibody, started when chronic infection is established, did not alter host resistance but increased tolerance. In conclusion, this study identifies IL-17-mediated response as a negative regulator of host tolerance during P. aeruginosa chronic airway infection.

AB - Resistance and tolerance mechanisms participate to the interplay between host and pathogens. IL-17-mediated response has been shown to be crucial for host resistance to respiratory infections, whereas its role in host tolerance during chronic airway colonization is still unclear. Here, we investigated whether IL-17-mediated response modulates mechanisms of host tolerance during airways chronic infection by P. aeruginosa. First, we found that IL-17A levels were sustained in mice at both early and advanced stages of P. aeruginosa chronic infection and confirmed these observations in human respiratory samples from cystic fibrosis patients infected by P. aeruginosa. Using IL-17a a'/a' or IL-17ra a'/a' mice, we found that the deficiency of IL-17A/IL-17RA axis was associated with: i) increased incidence of chronic infection and bacterial burden, indicating its role in the host resistance to P. aeruginosa; ii) reduced cytokine levels (KC), tissue innate immune cells and markers of tissue damage (pro-MMP-9, elastin degradation, TGF-β 1), proving alteration of host tolerance. Blockade of IL-17A activity by a monoclonal antibody, started when chronic infection is established, did not alter host resistance but increased tolerance. In conclusion, this study identifies IL-17-mediated response as a negative regulator of host tolerance during P. aeruginosa chronic airway infection.

UR - http://www.scopus.com/inward/record.url?scp=84970016009&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84970016009&partnerID=8YFLogxK

U2 - 10.1038/srep25937

DO - 10.1038/srep25937

M3 - Article

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 25937

ER -