Abstract
Human deep lung harbours discrete and dynamic microbiota profiles called pneumotypes, which are associated with specific immune response and lung health (Das et al. Nature Comm 2021). However, we know little about the direct interactions between lung bacteria and innate immune cells especially macrophages that share the same niche.
In this study, we aim to understand the recognition and inflammatory potential of human lung primary isolates by alveolar macrophages and also decipher underlying mechanisms. To this end, we have establised an alveolar macrophage-like cell model in vitro and validated using single cell mass cytometry. These cells along with HEK cells expressing TLR2 and TLR4 were exposed to lung bacteria followed by quantification by a NFkB activation reporter system.
Typically non-pathogenic lung bacteria and Small-artificial communities (SACs) partially resembling healthy human lung microbiota show differential inflammatory potential, recognition and gene expression in AM-like macrophages. A subset of these also showed protective effects against exacerbation of inflammation by lung pathogens like Staphylococcus aureus and Pseudomonas aeruginosa. Amongst these, isolates of Streptococcus show differential inflammatory response despite being phylogenetically closer. This effect was driven by a difference in peptidoglycan composition with no contribution by streptococcal capsule. Finally, the majority of lung bacteria triggered TLR2 reponse and elicited TNFα-independent contact dependent IL-8 secretion.
Hence, here we present a new alveolar macrophage model and novel interactions with human lung bacteria. We also highlight the importance lung commensals in inflammatory responses and immune homeostasis.
Footnotes
Cite this article as ERJ Open Research 2022; 8: Suppl. 8, 112.
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