New player identified in the innate immune response against bacterial pathogens

Researchers at KU Leuven Department of Cellular and Molecular Medicine (Leuven, Belgium) have discovered a new role for ion channels as a first line defence against bacterial infection.

When bacteria enter the human lung our immune system kick starts a powerful cascading immune response. However, this does not account fully for the immediate reaction.

In this present study, published in Nature Communications, researchers demonstrated that in airway epithelial cells (ECs) intracellular levels of Ca2+ increased upon application of lipopolysaccharides (LPS) – the main component of the Gram-negative cell wall.

This response occurs via ion channel-mediated mechanisms via activation of a transient receptor potential vanilloid 4 cation channel (TRPV4), which triggers rapid cell-intrinsic events.

Upon LPS challenge, TRPV4 instantly increases the beat frequency of cilia on ECs to clear the pathogen from the airways. The pathway also leads to the production of nitric oxide, which is bactericidal.

This protective immune pathway is distinct from the well-known innate immune response pathway of cytokine-mediated activation of immune cells.

The study discovered that mice lacking the TRPV4 suffered exacerbated ventilatory and inflammatory responses upon LPS application.

“Our study shows that our body’s strategy to fight off bacterial infections is not limited to previously identified immune pathways,” explains Karel Talavera Pérez (KU Leuven), one of the study’s lead authors “So-called TRPV4 ion channels play a role as well: they are essential to our body’s earliest defence mechanism against bacterial invasion. If we want to develop more effective treatments, these ion channels are well worth investigating in greater detail.”

Sources: Alpizar YA, Boonen B, Sanchez A et al. TRPV4 activation triggers protective responses to bacterial lipopolysaccharides in airway epithelial cells. Nat. Comms. 8(1) doi:10.1038/s41467-017-01201-3 (2017);


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