Published: 5 May 2022

Authors: Charlotte Rigauts, Juliana Aizawa, Steven L. Taylor, Geraint B. Rogers, Matthias Govaerts, Paul Cos, Lisa Ostyn, Sarah Sims, Eva Vandeplassche, Mozes Sze, Yves Dondelinger, Lars Vereecke, Heleen Van Acker, Jodie L. Simpson, Lucy Burr, Anne Willems, Michael M. Tunney, Cristina Cigana, Alessandra Bragonzi, Tom Coenye and Aurélie Crabbé

Source: This abstract has been sourced from NZ Respiratory Research Review Issue 204


    Background Chronic airway inflammation is the main driver of pathogenesis in respiratory diseases such as severe asthma, chronic obstructive pulmonary disease, cystic fibrosis (CF) and bronchiectasis. While the role of common pathogens in airway inflammation is widely recognised, the influence of other microbiota members is still poorly understood.

    Methods We hypothesised that the lung microbiota contains bacteria with immunomodulatory activity which modulate net levels of immune activation by key respiratory pathogens. Therefore, we assessed the immunomodulatory effect of several members of the lung microbiota frequently reported as present in CF lower respiratory tract samples.

    Results We show that Rothia mucilaginosa, a common resident of the oral cavity that is also often detectable in the lower airways in chronic disease, has an inhibitory effect on pathogen- or lipopolysaccharide-induced pro-inflammatory responses, in vitro (three-dimensional cell culture model) and in vivo (mouse model). Furthermore, in a cohort of adults with bronchiectasis, the abundance of Rothia species was negatively correlated with pro-inflammatory markers (interleukin (IL)-8 and IL-1β) and matrix metalloproteinase (MMP)-1, MMP-8 and MMP-9 in sputum. Mechanistic studies revealed that R. mucilaginosa inhibits NF-κB pathway activation by reducing the phosphorylation of IκBα and consequently the expression of NF-κB target genes.

    Conclusions These findings indicate that the presence of R. mucilaginosa in the lower airways potentially mitigates inflammation, which could in turn influence the severity and progression of chronic respiratory disorders.

    Link to abstract

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