Abstract
Non-typeable Haemophilus influenzae (NTHi) is a key pathogen in chronic respiratory diseases such as asthma and COPD, being associated with airway inflammation and increasing risk of exacerbation in these diseases. However, the mechanisms by which NTHi can colonise and persist in the human lung are not well understood. The aim of this project was therefore to gain a better understanding of the host-pathogen interactions in lung tissue incubated with NTHi.
Resected human lung tissue (n=5) was incubated with 5 x 106 colony forming units (CFU) NTHi for 24 h. Tissue infection was confirmed and quantified using fluorescence in situ hybridisation (FISH). Gene expression of inflammatory cytokines was performed using TaqMan RT-qPCR and cytokine release was assayed using a Luminex multiplex ELISA.
Infection with NTHi in lung tissue was confirmed by FISH, using a specific NTHi-Cy3 probe. There was a significant 17.2 fold increase in the gene expression of IL-1b (P=0.0080), a 3.5-fold increase in TNFa expression (P=0.0213) and a 2.7-fold increase in IL-6 expression (P=0.0261) in response to NTHi infection. There was a significant increase in the release of IL-1β (median uninfected 143.4 pg/ml vs infected 3868 pg/ml: P=0.0313) into the supernatants of infected tissues were also observed. Further cytokines that were significantly released in response to infection by lung tissue include IL-6, IL-10, IL-12, IL-17A, IL-17C, IL23 and IL-27.
In conclusion, we have developed a relevant human lung model for evaluating the host innate response to NTHi. Such a model will provide opportunities for identifying mechanisms of NTHi persistence in the lung and testing novel therapeutics that target this host-pathogen axis.
Footnotes
Cite this article as ERJ Open Research 2022; 8: Suppl. 8, 46.
This article was presented at the 2022 ERS Lung Science Conference, in session “Poster Session 2”.
This is an ERS Lung Science Conference abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2022
