Respiration Section Fall Newsletter

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 (American Journal of Physiology - Lung Cellular and Molecular Physiology, 2015; 309:L902) demonstrated that ASC-deficient mice still produce abundant IL-1β in response to infection.  Interestingly, these authors demonstrate that neutrophils are able to produce IL-1β independently of ASC, but still dependent on caspase 1.  These interesting results shed new light on the role that neutrophils play in regulating inflammatory cell influx and immunopathology, but as all good science does, these results also raise new questions.  Exactly how caspase 1 regulates IL-1β cleavage and activation in the absence of the cannonical NLRC4-ASC-containing inflammasome will be the subject of future investigations.

Associate Editor AJP-Lung, Beth Moore

APSselect October 2015 selection

AJP-Lung would like to recognize Dr. Brian Graham and his colleagues. Their article "Severe pulmonary hypertension is associated with altered right ventricle metabolic substrate uptake

" was chosen for APSselect October 2015.  You can access their paper, here.

Data Presentation

The editors at AJP Lung have been thinking a lot about data presentation.  Many scientists present their results by showing bar graphs that plot the mean plus or minus the standard error of the mean (mean ± SEM).  The advantage of this approach is that bar graphs are neat and easy to read, but it is also appreciated that this method of presenting data can mask some important attributes and potentially may be misinterpreted.  Recently, there was a very nice article by Harvey Motulsky, from Graphpad software, the maker of a commonly used data analysis program that highlights some important misconceptions about data analysis.  The article is available as open access (Pharmacol Res Perspect. 2015 Feb;3(1):e00093) and the link is provided here: Motulsky article .  It is especially interesting to consider figure 5 of the paper, which shows the same data set graphed 6 ways.  Looking at this figure, it can be appreciated that plotting mean ± SEM gives little insight into the variability in the data set.  It also may mask different sample sizes in some cases.  Some journals have editorial policies to insist that data be presented as scatter plots.  While AJP Lung has not decided on such an editorial policy at this time, we do want to encourage authors to think about how they present their data and to do so in the most transparent manner possible.  In the meantime, Happy Fall!