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Multiple regulated neutrophil cell death programs contribute to host defense against infections. However, despite expressing all necessary inflammasome components, neutrophils are thought to be generally defective in Caspase-1-dependent pyroptosis. By screening different bacterial species, we found that several Pseudomonas aeruginosa ( P . aeruginosa ) strains trigger Caspase-1-dependent pyroptosis in human and murine neutrophils. Notably, deletion of Exotoxins U or S in P . aeruginosa enhanced neutrophil death to Caspase-1-dependent pyroptosis, suggesting that these exotoxins interfere with this pathway. Mechanistically, P . aeruginosa Flagellin activates the NLRC4 inflammasome, which supports Caspase-1-driven interleukin (IL)-1β secretion and Gasdermin D (GSDMD)-dependent neutrophil pyroptosis. Furthermore, P . aeruginosa -induced GSDMD activation triggers Calcium-dependent and Peptidyl Arginine Deaminase-4-driven histone citrullination and translocation of neutrophil DNA into the cell cytosol without inducing extracellular Neutrophil Extracellular Traps. Finally, we show that neutrophil Caspase-1 contributes to IL-1β production and susceptibility to pyroptosis-inducing P . aeruginosa strains in vivo . Overall, we demonstrate that neutrophils are not universally resistant for Caspase-1-dependent pyroptosis.

Abstract Dietary supplementations with n-3 polyunsaturated fatty acid (PUFA) have been explored in autism spectrum disorder (ASD) but their efficiency and potential in ameliorating cardinal symptoms of the disease remain elusive. Here, we compared a n-3 long-chain (LC) PUFA dietary supplementation (n-3 supp) obtained from fatty fish with a n-3 PUFA precursor diet (n-3 bal) obtained from plant oils in the valproic acid (VPA, 450 mg/kg at E12.5) ASD mouse model starting from embryonic life, throughout lactation and until adulthood. Maternal and offspring behaviors were investigated as well as several VPA-induced ASD biological features: cerebellar Purkinje cell (PC) number, inflammatory markers, gut microbiota, and peripheral and brain PUFA composition. Developmental milestones were delayed in the n-3 supp group compared to the n-3 bal group in both sexes. Whatever the diet, VPA-exposed offspring did not show ASD characteristic alterations in social behavior, stereotypies, PC number, or gut microbiota dysbiosis while global activity, gait, peripheral and brain PUFA levels as well as cerebellar TNF-alpha levels were differentially altered by diet and treatment according to sex. The current study provides evidence of beneficial effects of n-3 PUFA based diets, including one without LCPUFAs, on preventing several behavioral and cellular symptoms related to ASD.

Introduction: Positive urine sample is a frequent finding in post-chemotherapy febrile neutropenia (FN) and can lead to prolonged antibiotic therapy. The aim of this study was to assess the outcome of bacteriuria episodes in FN patients receiving targeted antibiotic therapy.Materials and methods: A multi-centric retrospective study was conducted over a four-year period (2014-2019) on systematic urinalysis. All consecutive first bacteriuria episodes (≤ 2 bacteria with at least ≥ 103 CFU/mL) during FN in hospitalized adult patients for hematological malignancies were included. Relapse and recurrence were defined by fever or urinary tract symptoms (UTS) with the same bacterial subspecies in urine occurring ≤ 7 days and ≤ 30 days, respectively, after antibiotic discontinuation. Mortality rate was determined at 30 days. Targeted antibiotic therapy ≤ 10 days for women and ≤ 14 for men was considered as short course.Results: Among 97 patients, 105 bacteriuria episodes on systematic urinalysis were analyzed; 67.6% occurred in women, 41.9% in AML patients, 17.1% were bacteremic, 14.2% presented with UTS, and 61.9% were treated with short-course antibiotic treatment. One death was reported. In men, no relapse/recurrence was noted, even in the short-course antibiotic group. In women, 2.8% of episodes treated with short-course antibiotic led to relapse or recurrence.Conclusions: Relapse, recurrence, and mortality were uncommon events in FN patients experiencing bacteriuria episode, whatever the antibiotic duration. To distinguish asymptomatic bacteriuria from infection remained challenging in women. In men, systematic urinalysis at onset of FN could be useful.