Renal Sodium Gradient Orchestrates a Dynamic Antibacterial Defense Zone.

Lower urinary tract infections are among the most common human bacterial infections, but extension to the kidneys is rare. This has been attributed to mechanical forces, such as urine flow, that prevent the ascent of bladder microbes. Here, we show that the regional hypersalinity, required for the kidney's urine-concentrating function, instructs epithelial cells to produce chemokines that localize monocyte-derived mononuclear phagocytes (MNPs) to the medulla. This hypersaline environment also increases the intrinsic bactericidal and neutrophil chemotactic activities of MNPs to generate a zone of defense. Because MNP positioning and function are dynamically regulated by the renal salt gradient, we find that patients with urinary concentrating defects are susceptible to kidney infection. Our work reveals a critical accessory role for the homeostatic function of a vital organ in optimizing tissue defense.

Phosphorylated STAT3 suppresses microRNA-19b/1281 to aggravate lung injury in mice with type 2 diabetes mellitus-associated pulmonary tuberculosis.

Type 2 diabetes mellitus (T2DM) is a risk factor for pulmonary tuberculosis (PTB) and increased mortality. This work focused on the functions of phosphorylated STAT3 in lung injury in mouse with T2DM-associated PTB and the molecules involved. A mouse model with T2DM-PTB was induced by administrations of streptozotocin, nicotinamide and mycobacterium tuberculosis (Mtb). A pSTAT3-specific inhibitor AG-490 was given into mice and then the lung injury in mice was observed. The molecules involved in AG-490-mediated events were screened out. Altered expression of miR-19b, miR-1281 and NFAT5 was introduced to identify their involvements and roles in lung injury and PTB severity in the mouse model. Consequently, pSTAT3 expression in mice with T2DM-associated PTB was increased. Down-regulation of pSTAT3 by AG-490 prolonged the lifetime of mice and improved the histopathologic conditions, and inhibited the fibrosis, inflammation, Mtb content and number of apoptotic epithelial cells in mouse lung tissues. pSTAT3 transcriptionally suppressed miR-19b/1281 expression to up-regulate NFAT5. Inhibition of miR-19b/1281 or up-regulation of NFAT5 blocked the protective roles of AG-490 in mouse lung tissues. To conclude, this study evidenced that pSTAT3 promotes NFAT5 expression by suppressing miR-19b/1281 transcription, leading to lung injury aggravation and severity in mice with T2DM-associated PTB.