Airway basal stem cells are necessary for the maintenance of functional intraepithelial airway macrophages.

Adult stem cells play a crucial role in tissue homeostasis and repair through multiple mechanisms. In addition to being able to replace aged or damaged cells, stem cells provide signals that contribute to the maintenance and function of neighboring cells. In the lung, airway basal stem cells also produce cytokines and chemokines in response to inhaled irritants, allergens, and pathogens, which affect specific immune cell populations and shape the nature of the immune response. However, direct cell-to-cell signaling through contact between airway basal stem cells and immune cells has not been demonstrated. Recently, a unique population of intraepithelial airway macrophages (IAMs) has been identified in the murine trachea. Here, we demonstrate that IAMs require Notch signaling from airway basal stem cells for maintenance of their differentiated state and function. Furthermore, we demonstrate that Notch signaling between airway basal stem cells and IAMs is required for antigen-induced allergic inflammation only in the trachea where the basal stem cells are located whereas allergic responses in distal lung tissues are preserved consistent with a local circuit linking stem cells to proximate immune cells. Finally, we demonstrate that IAM-like cells are present in human conducting airways and that these cells display Notch activation, mirroring their murine counterparts. Since diverse lung stem cells have recently been identified and localized to specific anatomic niches along the proximodistal axis of the respiratory tree, we hypothesize that the direct functional coupling of local stem cell-mediated regeneration and immune responses permits a compartmentalized inflammatory response.

Notch3 Deficiency Attenuates Pulmonary Fibrosis and Impedes Lung-Function Decline.

Fibroblast activation includes differentiation to myofibroblasts and is a key feature of organ fibrosis. The Notch pathway has been involved in myofibroblast differentiation in several tissues, including the lung. Here, we identify a subset of collagen-expressing cells in the lung that exhibit Notch3 activity at homeostasis. After injury, this activation increases, being found in αSMA-expressing myofibroblasts in the mouse and human fibrotic lung. Although previous studies suggest a contribution of Notch3 in stromal activation, in vivo evidence of the role of Notch3 in lung fibrosis remains unknown. In this study, we examine the effects of Notch3 deletion in pulmonary fibrosis and demonstrate that Notch3-deficient lungs are protected from lung injury with significantly reduced collagen deposition after bleomycin administration. The induction of profibrotic genes is reduced in bleomycin-treated Notch3-knockout lungs that consistently present fewer αSMA-positive myofibroblasts. As a result, the volume of healthy lung tissue is higher and lung function is improved in the absence of Notch3. Using in vitro cultures of lung primary fibroblasts, we confirmed that Notch3 participates in their survival and differentiation. Thus, Notch3 deficiency mitigates the development of lung fibrosis because of its role in mediating fibroblast activation. Our findings reveal a previously unidentified mechanism underlying lung fibrogenesis and provide a potential novel therapeutic approach to target pulmonary fibrosis.

Evaluation of Combined Disinfection Methods for Reducing Escherichia coli O157:H7 Population on Fresh-Cut Vegetables.

Most current disinfection strategies for fresh-cut industry are focused on the use of different chemical agents; however, very little has been reported on the effectiveness of the hurdle technology. The effect of combined decontamination methods based on the use of different sanitizers (peroxyacetic acid and chlorine dioxide) and the application of pressure (vacuum/positive pressure) on the inactivation of the foodborne pathogen E. coli O157:H7 on fresh-cut lettuce (Lactuca sativa) and carrots (Daucus carota) was studied. Fresh produce, inoculated with E. coli O157:H7, was immersed (4 °C, 2 min) in tap water (W), chlorine water (CW), chlorine dioxide (ClO2: 2 mg/L) and peroxyacetic acid (PAA: 100 mg/L) in combination with: (a) vacuum (V: 10 mbar) or (b) positive pressure application (P: 3 bar). The product quality and antimicrobial effects of the treatment on bacterial counts were determined both in process washing water and on fresh-cut produce. Evidence obtained in this study, suggests that the use of combined methods (P/V + sanitizers) results in a reduction on the microorganism population on produce similar to that found at atmospheric pressure. Moreover, the application of physical methods led to a significant detrimental effect on the visual quality of lettuce regardless of the solution used. Concerning the process water, PAA proved to be an effective alternative to chlorine for the avoidance of cross-contamination.