Kidney intercalated cells are involved in acid-base homeostasis via vacuolar ATPase expression. Here we report six human intercalated cell subtypes, including hybrid principal-intercalated cells identified from single cell transcriptomics. Phagosome maturation is a biological process that increases in biological pathway analysis rank following exposure to uropathogenicEscherichia coliin two of the intercalated cell subtypes. Real time confocal microscopy visualization of murine renal tubules perfused with green fluorescent protein expressingEscherichia colior pHrodo GreenE. coliBioParticles demonstrates that intercalated cells actively phagocytose bacteria then acidify phagolysosomes. Additionally, intercalated cells have increased vacuolar ATPase expression following in vivo experimental UTI. Taken together, intercalated cells exhibit a transcriptional response conducive to the kidney’s defense, engulf bacteria and acidify the internalized bacteria. Intercalated cells represent an epithelial cell with characteristics of professional phagocytes like macrophages.

Antimicrobial peptides (AMPs) are critical to the protection of the urinary tract of humans and other animals from pathogenic microbial invasion. AMPs rapidly destroy pathogens by disrupting microbial membranes and/or augmenting or inhibiting the host immune system through a variety of signaling pathways. We have previously demonstrated that alpha-defensins 1-3 ( DEFA1A3 ) are AMPs expressed in the epithelial cells of the human kidney collecting duct in response to uropathogens. We also demonstrated that DNA copy number variations in the DEFA1A3 locus are associated with UTI and pyelonephritis risk. Because DEFA1A3 is not expressed in mice, we utilized human DEFA1A3 gene transgenic mice ( DEFA 4/4 ) to further elucidate the biological relevance of this locus in the murine urinary tract. We demonstrate that the kidney transcriptional and translational expression pattern is similar in humans and the human gene transgenic mouse upon uropathogenic Escherichia coli (UPEC) stimulus in vitro and in vivo. We also demonstrate transgenic human DEFA 4/4 gene mice are protected from UTI and pyelonephritis under various UPEC challenges. This study serves as the foundation to start the exploration of manipulating the DEFA1A3 locus and alpha-defensins 1-3 expression as a potential therapeutic target for UTIs and other infectious diseases.

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Carbonic anhydrase II knockout ( Car2−/−) mice have depleted numbers of renal intercalated cells, which are increasingly recognized to be innate immune effectors. We compared pyelonephritis susceptibility following reciprocal renal transplantations between Car2−/− and wild-type mice. We examined the effect of pharmacological CA suppression using acetazolamide in an experimental murine model of urinary tract infection. Car2−/− versus wild-type mice were compared for differences in renal innate immunity. In our transplant scheme, mice lacking CA-II in the kidney had increased pyelonephritis risk. Mice treated with acetazolamide had lower kidney bacterial burdens at 6 h postinfection, which appeared to be due to tubular flow from diuresis because comparable results were obtained when furosemide was substituted for acetazolamide. Isolated Car2−/− kidney cells enriched for intercalated cells demonstrated altered intercalated cell innate immune gene expression, notably increased calgizzarin and insulin receptor expression. Intercalated cell number and function along with renal tubular flow are determinants of pyelonephritis risk.

Background: The occurrence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated coronavirus disease 2019 have profoundly affected adult kidney disease patients. In contrast, pediatric solid organ transplant recipients, including pediatric kidney transplant (KT) recipients, do not seem to be at particularly higher risk for SARS-CoV-2 infection or for severe COVID-19 disease. This patient population might be protected by certain mechanisms, such as the immunosuppressive medications with their anti-inflammatory properties or simply being well-versed in self-protection techniques. Assessing SARS-CoV-2 antibody serologies could potentially help understand why this patient population is apparently spared from severe SARS-CoV-2 clinical courses.Objective: To examine SARS-CoV-2 serologic status in a cohort of pediatric KT recipients.Methods: SARS-CoV-2 anti-spike IgG and IgM antibodies were measured by three different methods in pediatric KT recipients coming for routine clinic visits immediately post-confinement in May-June of 2020. The patients were considered seroconverted if SARS-CoV-2 antibodies were positive by 2/3 methods and weak positive/indeterminate if positive by 1/3.Results: Thirty-one patients were evaluated (about 1/3 of our institution's pediatric KT population). One patient seroconverted, while three were considered weak positive/indeterminate. None were symptomatic and none had nasopharyngeal PCR confirmed SARS-CoV-2 disease.Conclusions: Seroconversion to SARS-CoV-2 was rare in this population and likely reflects the social distancing practiced by these patients. The results will serve as a foundation for a future longitudinal study to evaluate the long-term emergence and persistence of antibodies in this population and may inform studies of response to a future vaccine.