Mucosal lymphoid cells key to S. pneumoniae defence
medwireNews: Type 3 innate lymphoid cells (ILC3) in the lung mucosa are activated early in the course of infection with Streptococcus pneumoniae and are a major source of interleukin (IL)-22 production, research reveals.
The findings suggest that “boosting lung ILC3 might represent an interesting strategy to fight respiratory bacterial infections”, say the study authors writing in The Journal of Infectious Diseases.
ILC3 is prevalent at mucosal sites and is known to be a key player in antimicrobial defence in the intestines, through the production of IL-22 and IL-17.
To investigate the role of ILC3 in the respiratory tract, Jean-Claude Sirard (Institut Pasteur de Lille, France) and co-workers performed a series of experiments in mice that were inoculated with S. pneumoniae serotype 1.
The research showed that lung tissue from healthy mice produced IL-22 and IL-17 in response to IL-23 stimulation and that this effect was enhanced in lungs that had been inoculated with S. pneumoniae.
Further study revealed that ILC3 was the major source of IL-22 and IL-17 in the lung but that levels of these cytokines induced by S. pneumoniae infection were not sufficient to trigger antimicrobial defence.
The team next administered flagellin, a Toll-like receptor 5 agonist, to the mice at the same time as S. pneumoniae inoculation, finding that this significantly boosted IL-22 and IL-17 production in the respiratory mucosa and also increased Il22 and Il17a and Il17f transcript levels.
“Of importance, the transcriptional activation was not only exacerbated but also accelerated, with a response detected as soon as 2 hours after treatment,” Sirard and co-authors write.
Finally, they showed that administration of flagellin protected mice against S. pneumoniae infection, as indicated by an improved survival rate and reduced bacterial load in the lung. Further study confirmed that this protection was driven by IL-22.
The researchers say that their findings support a role for ILC3 in flagellin-mediated defences, acting through the production of IL-17/IL-22, in the context of respiratory infection.
They conclude: “Altogether, our data provide evidence that lung ILC3 and IL-22 are interesting targets for immune-based therapies against respiratory infection.”
medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2014
By Joanna Lyford, Senior medwireNews Reporter