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 language | English |
|---|---|
| Article number | 25937 |
| Journal | Scientific Reports |
| Volume | 6 |
| DOIs | |
| Publication status | Published - May 18 2016 |
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ASJC Scopus subject areas
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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 journal › Article
}
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.
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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 -