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

ASJC Scopus subject areas

  • General

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