02319nas a2200325   4500000000100000000000100001008004100002260000900043653002300052653002000075653001800095653001800113653002400131100002600155700001700181700002200198700001800220700002600238700001900264700001700283700002600300700002300326700002000349245007500369856006700444300001200511490000600523520145000529022001401979       2019                            d  c201910aepithelial barrier10ain vitro assays10amicrofluidics10aorgan-on-chip10apulmonary infection1 aArbel Artzy-Schnirman1 aHikaia Zidan1 aShani Elias-Kirma1 aLee Ben-Porat1 aJanna Tenenbaum-Katan1 aPatrick Carius1 aRamy Fishler1 aNicole Schneider-Daum1 aClaus-Michael Lehr1 aJosué Sznitman00aCapturing the Onset of Bacterial Pulmonary Infection in Acini-On-Chips  uhttps://onlinelibrary.wiley.com/doi/abs/10.1002/adbi.201900026  a19000260 v33 aBacterial invasion of the respiratory system leads to complex immune responses. In the deep alveolar regions, the first line of defense includes foremost the alveolar epithelium, the surfactant-rich liquid lining, and alveolar macrophages. Typical in vitro models come short of mimicking the complexity of the airway environment in the onset of airway infection; among others, they neither capture the relevant anatomical features nor the physiological flows innate of the acinar milieu. Here, novel microfluidic-based acini-on-chips that mimic more closely the native acinar airways at a true scale with an anatomically inspired, multigeneration alveolated tree are presented and an inhalation-like maneuver is delivered. Composed of human alveolar epithelial lentivirus immortalized cells and macrophages-like human THP-1 cells at an air–liquid interface, the models maintain critically an epithelial barrier with immune function. To demonstrate, the usability and versatility of the platforms, a realistic inhalation exposure assay mimicking bacterial infection is recapitulated, whereby the alveolar epithelium is exposed to lipopolysaccharides droplets directly aerosolized and the innate immune response is assessed by monitoring the secretion of IL8 cytokines. These efforts underscore the potential to deliver advanced in vitro biosystems that can provide new insights into drug screening as well as acute and subacute toxicity assays.  a2366-7478