Monday, October 19, 2015

The role that neutrophils play in regulating inflammatory cell influx and immunopathology

Pseudomonas aeruginosa is an important Gram-negative pathogen for both hospital-acquired infections and patients with lung diseases like Cystic Fibrosis.  One thing to note about P. aeruginosa is that this bacterial infection often causes a significant influx of neutrophils.  Certainly these innate immune cells play an important role in helping to ingest and kill the pathogen, but it is also appreciated that neutrophils can promote tissue damage, and may contribute to the pathogenesis of some autoimmune diseases.  Exactly how neutrophils promote the “immunopathology” that can occur following some infections is not clear.  A new article in AJP Lung this month provides compelling new evidence for the importance of neutrophils in producing the cytokine, interleukin (IL)-1β and the mechanism for how they are activated.  IL-1β production is critical for initiating inflammatory cell recruitment and activation, but prolonged IL-1β production can lead to immunopathology.  What is most intriguing about this paper is the observation that the molecular signaling mechanisms that lead to IL-1β production in macrophages vs. neutrophils are completely different despite the fact that these are both innate immune cell types responsible for initial engagement with bacterial pathogens.  Macrophages generally secrete IL-1β following activation of the inflammasome containing NLRC4, ASC and caspase-1.   Given this, one would have predicted that mice deficient in ASC, one of the NLRC4 inflammasome components, would be prevented from IL-1β secretion in response to P. aeruginosa infection. However, Patankar et al. in this issue (

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