@article {Saliu00614-2020, author = {Fabio Saliu and Giulia Rizzo and Alessandra Bragonzi and Lisa Cariani and Daniela M. Cirillo and Carla Colombo and Valeria Dacc{\`o} and Daniela Girelli and Sara Rizzetto and Barbara Sipione and Cristina Cigana and Nicola I. Lor{\`e}}, title = {Chronic infection by nontypeable Haemophilus influenzae fuels airway inflammation}, volume = {7}, number = {1}, elocation-id = {00614-2020}, year = {2021}, doi = {10.1183/23120541.00614-2020}, publisher = {European Respiratory Society}, abstract = {Nontypeable Haemophilus influenzae (NTHi) is commonly isolated from airways of patients suffering from chronic respiratory diseases, such as COPD or cystic fibrosis (CF). However, to what extent NTHi long-term infection contributes to the lung inflammatory burden during chronic airway disease is still controversial.Here, we exploited human respiratory samples from a small cohort of CF patients and found that patients chronically infected with NTHi had significantly higher levels of interleukin (IL)-8 and CXCL1 than those who were not infected. To better define the impact of chronic NTHi infection in fuelling inflammatory response in chronic lung diseases, we developed a new mouse model using both laboratory and clinical strains. Chronic NTHi infection was associated with chronic inflammation of the lung, characterised by recruitment of neutrophils and cytokine release keratinocyte-derived chemokine (KC), macrophage inflammatory protein 2 (MIP-2), granulocyte colony-stimulating factor (G-CFS), IL-6, IL-17A and IL-17F) at 2 and 14 days post-infection. An increased burden of T-cell-mediated response (CD4+ and γδ cells) and higher levels of pro-matrix metalloproteinase 9 (pro-MMP9), known to be associated with tissue remodelling, were observed at 14 days post-infection. Of note we found that both CD4+IL-17+ cells and levels of IL-17 cytokines were enriched in mice at advanced stages of NTHi chronic infection. Moreover, by immunohistochemistry we found CD3+, B220+ and CXCL-13+ cells localised in bronchus-associated lymphoid tissue-like structures at day 14.Our results demonstrate that chronic NTHi infection exerts a pro-inflammatory activity in the human and murine lung and could therefore contribute to the exaggerated burden of lung inflammation in patients at risk.The pathological impact of long-term infection by nontypeable Haemophilus influenzae (NTHi) is still debated. Chronic NTHi infection fuels lung inflammation in human samples and in a new mouse model of bacterial long-term persistence. https://bit.ly/3lvyvge}, URL = {https://openres.ersjournals.com/content/7/1/00614-2020}, eprint = {https://openres.ersjournals.com/content/7/1/00614-2020.full.pdf}, journal = {ERJ Open Research} }