The role of TLRs in neutrophil activation

Neutrophils are key innate immune effector cells that are rapidly recruited to sites of infection and inflammation to provide early defence against invading microorganisms. This function is facilitated by the expression of Toll-like receptor (TLR) family members by neutrophils, allowing the recognition of an extensive repertoire of pathogen-associated molecular patterns (PAMPs) and thus triggering the response to invading pathogens. TLR activation leads to important cellular processes including reactive oxygen species (ROS) generation, cytokine production and increased survival, all of which can contribute to the pathogenesis of chronic inflammation when signalling becomes dysregulated. In turn, inflammation and tissue injury results in the release of endogenous TLR ligands, known as damage-associated molecular patterns (DAMPs), which are a rapidly growing class of potent inflammatory stimuli. DAMPs act in an autocrine manner, alerting the host of damage, but can also amplify inflammation leading to further tissue damage. This review highlights recent literature on neutrophil TLR function and regulation during disease, and provides an overview of the recently emerging area of neutrophil responses to DAMPs.

► Neutrophil TLR expression is modulated by pathogens and during disease.
► Neutrophils are activated in response to DAMPs in a TLR-dependent manner.
► TLR activation leads to neutrophilic inflammation in vitro and in vivo.
► Therapeutically blocking TLRs have the potential to reduce neutrophilic inflammation in vivo.