Toll-Like Receptor Signaling Critical to Lung Immune Defense

A recent study has detailed the process by which the lungs regulate the immune response that protects them from airborne pathogens.

Investigators at Columbia University (New York, NY, USA) studied the activity of lung epithelial cells in a mouse model. They reported in the January 22, 2009, edition of the journal Cell Host & Microbe that in order for the immune system to deal with a pathogenic incursion in the lungs, polymorphonuclear leukocytes (PMNs) first have to be recruited from the immune system and transferred into the lungs.

To reach the site of infection, PMNs must pass through epithelial junctions. The current study demonstrated that calcium fluxes generated by toll-like receptor (TLR2) signals activated calpains, calcium-dependent cysteine proteases. These activated calpains cleaved the transmembrane junction proteins occludin and E-cadherin without breaching the integrity of the epithelial barrier.

The investigators showed that calpain inhibitors decreased PMN transfer through the epithelial barrier in response to TLR2 agonists both in vitro and in a mouse model of a bacterial lung infection. Thus, TLR2 signaling in the airway not only induced chemokine expression to recruit PMNs, but also initiated cleavage of junction proteins to accommodate transport of the recruited PMNs.

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