RT Journal Article
SR Electronic
T1 A high-salt diet compromises antibacterial neutrophil responses through hormonal perturbation
JF Science Translational Medicine
FD American Association for the Advancement of Science
SP eaay3850
DO 10.1126/scitranslmed.aay3850
VO 12
IS 536
A1 Jobin, Katarzyna
A1 Stumpf, Natascha E.
A1 Schwab, Sebastian
A1 Eichler, Melanie
A1 Neubert, Patrick
A1 Rauh, Manfred
A1 Adamowski, Marek
A1 Babyak, Olena
A1 Hinze, Daniel
A1 Sivalingam, Sugirthan
A1 Weisheit, Christina
A1 Hochheiser, Katharina
A1 Schmidt, Susanne V.
A1 Meissner, Mirjam
A1 Garbi, Natalio
A1 Abdullah, Zeinab
A1 Wenzel, Ulrich
A1 Hölzel, Michael
A1 Jantsch, Jonathan
A1 Kurts, Christian
YR 2020
UL http://stm.sciencemag.org/content/12/536/eaay3850.abstract
AB Sodium chloride (salt) has been shown to invigorate immune responses in various contexts. In contrast, Jobin et al. now show that salt can impair neutrophil antibacterial responses. Mice on a high-salt diet experienced exacerbated E. coli kidney or systemic Listeria monocytogenes infections due to reduced capacity of neutrophils to kill ingested bacteria. The neutrophil deficiencies were not due directly to salt or urea but instead were dependent on salt-induced hyperglucocorticoidism. In addition, neutrophils from healthy volunteers were less capable of controlling bacteria ex vivo after consumption of a high-salt diet. Given that the typical Western diet is replete with salt, these findings reveal that people might be making themselves more vulnerable to bacterial infections.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.