The Western diet is rich in salt, which poses various health risks. A high-salt diet (HSD) can stimulate immunity through the nuclear factor of activated T cells 5 (Nfat5)–signaling pathway, especially in the skin, where sodium is stored. The kidney medulla also accumulates sodium to build an osmotic gradient for water conservation. Here, we studied the effect of an HSD on the immune defense against uropathogenic E. coli–induced pyelonephritis, the most common kidney infection. Unexpectedly, pyelonephritis was aggravated in mice on an HSD by two mechanisms. First, on an HSD, sodium must be excreted; therefore, the kidney used urea instead to build the osmotic gradient. However, in contrast to sodium, urea suppressed the antibacterial functionality of neutrophils, the principal immune effectors against pyelonephritis. Second, the body excretes sodium by lowering mineralocorticoid production via suppressing aldosterone synthase. This caused an accumulation of aldosterone precursors with glucocorticoid functionality, which abolished the diurnal adrenocorticotropic hormone–driven glucocorticoid rhythm and compromised neutrophil development and antibacterial functionality systemically. Consistently, under an HSD, systemic Listeria monocytogenes infection was also aggravated in a glucocorticoid-dependent manner. Glucocorticoids directly induced Nfat5 expression, but pharmacological normalization of renal Nfat5 expression failed to restore the antibacterial defense. Last, healthy humans consuming an HSD for 1 week showed hyperglucocorticoidism and impaired antibacterial neutrophil function. In summary, an HSD suppresses intrarenal neutrophils Nfat5-independently by altering the local microenvironment and systemically by glucocorticoid-mediated immunosuppression. These findings argue against high-salt consumption during bacterial infections.

We studied the effects of norepinephrine on solute transport and oxidative metabolism in proximal tubules. Norepinephrine (10(-6) M) in the bath stimulated fluid absorption (Jv) by proximal convoluted tubules from 0.76 +/- 0.10 to 1.01 +/- 0.11 nl X mm-1 X min-1 (P less than 0.001). Bicarbonate, chloride, and phosphate transport also increased in proportion to the increases in Jv. Norepinephrine increased ouabain-sensitive oxygen consumption (QO2) in suspensions of cortical tubules by 1.3 nmol X mg protein-1 X min-1 and had no effect on ouabain-insensitive QO2 or mitochondrial respiration. Na+-K+-ATPase activity in basolateral membranes prepared from cortical homogenates incubated with norepinephrine increased from 277.1 +/- 34.9 to 411.1 +/- 38.6 nmol Pi X mg protein-1 X min-1 (P less than 0.005). Norepinephrine also increased Na+-K+-ATPase activity of cortical homogenates by 72% but had no effect on Na+-K+-ATPase if added directly to purified basolateral membranes. These studies show that norepinephrine stimulates solute transport in the proximal tubule by increasing Na+-K+-ATPase activity indirectly through some component or components of the adrenergic receptor system.

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide. Humans evolved various immune-dependent and independent defense mechanisms, while pathogens evolved multiple virulence factors to fight back. This article summarizes recent findings regarding the arms race between hosts and pathogens in UTIs. It was recently reported that macrophage subsets regulate neutrophil-mediated defense in primary UTIs but seem to subvert adaptive immunity upon re-infection. Moreover, some bacterial strains can survive inside macrophages, leading to recurrent infections. Inflammasome activation results in infected host cell death and pathogen release, facilitating the removal of intracellular bacteria. As a counteraction, some bacteria evolved mechanisms to disrupt inflammasome activation. Mucosal-associated invariant T cells are further effectors that can lyse infected epithelial cells and release intracellular bacteria. Once released, the bacteria are phagocytosed by neutrophils. However, some bacteria can inhibit neutrophil migration and deprive neutrophils of nutrients. Furthermore, the complement system, considered generally bactericidal, is exploited by the bacteria for cellular invasion. Another weapon against UTI is antimicrobial peptides, e.g. ribonuclease 7, but its production is inhibited by certain bacterial strains. Thus the arms race in UTI is ongoing, and knowing the enemy's methods can help in developing new drugs to win the race.

Conjunctiva-associated tissue (CALT) is assumed to play a crucial role in the immune system of the ocular surface. Its function in several ocular surface diseases (OSD) is still not fully understood. This study investigates the function of CALT in mouse models of dry-eye disease and ocular allergy. Since antigen-presentation is the central similarity in the pathologies, this study focuses on antigen-presentation in CALT Morphology and the expression of CALT, which was investigated in mice after induction of dry-eye, ocular allergy, topical antigen-stimulation, and after local depletion of phagocytic cells. Antigen uptake was investigated after the application of fluorescent ovalbumin (OVA). OSD influences the appearance and morphology of CALT in a disease-dependent manner. Ocular allergy leads to an increase and dry-eye disease to a decrease in number and size of CALT. The development of CALT is dependent on the presence of APCs. Professional APCs are present in CALT, and soluble antigen is transported into the follicle. CALT appearance is disease-specific and indicative of differing functions. Although the specific involvement of CALT in OSD needs further study, the existence of functional APCS and antigen-uptake supports the hypothesis that CALT is an immunological key player at the ocular surface.

To ascertain whether Na+ gradient-stimulated 32Pi uptake was demonstrable in renal basolateral membrane vesicles, we measured 32Pi uptake in basolateral membrane suspensions isolated from canine renal cortex and compared solute uptake in basolateral suspensions with that measured in brush border suspensions. Measurements revealed Na+ gradient-dependent 32Pi transport in basolateral preparations. D-[3H] Glucose uptakes in basolateral suspensions were not stimulated by the Na+ gradient in contrast to findings in brush border suspensions. Na+ gradient-dependent 32Pi transport in basolateral suspensions was electrogenic in contrast to that measured in brush border preparations. Unlike 32Pi uptake in brush border preparations, Na+ gradient-dependent 32Pi uptake in basolateral suspensions did not increase as extravesicular pH was increased from 6.5 to 7.5. Na+ gradient-dependent 32Pi uptake in basolateral membranes showed saturation over the range of [Pi] from 5 to 100 microM (apparent Km, 14 +/- 2 microM; apparent Vmax, 34 +/- 2 pmol Pi X mg protein-1 X 30s-1). Our findings are compatible with the presence of an electrogenic Na+-Pi cotransporter in the canine proximal tubular basolateral membrane.