Budiman, T. | bioRxiv Science

bioRxiv2025

Spatial analysis reveals the cellular microenvironments and mechanisms of inflammation and kidney injury in acute interstitial nephritis

Acute interstitial nephritis (AIN) causes 15-20% of all acute kidney injury cases but lacks effective therapies beyond corticosteroids. Using high-resolution imaging mass cytometry and single-cell spatial transcriptomics to analyze human kidney biopsies with AIN, non-immunologic acute tubular injury (ATI), and reference tissue, the CXCL9-CXCR3 axis was identified as the defining immunologic signature of AIN, with 44-fold higher predicted CXCL9-CXCR3 interactions than ATI, creating homotypic inflammatory T cell amplification networks concentrated in lymphoid aggregates. C3AR1+ immune cells were enriched in peritubular neighborhoods of complement 3-expressing injured tubule cells, predominantly VCAM1+ injured proximal tubules, linking tubular injury to immune activation in AIN. Nicotinamide phosphoribosyltransferase (NAMPT) was the strongest predictor of VCAM1+ tubular microenvironments, with expression by both injured tubules and surrounding immune cells coordinating metabolic-inflammatory niches. These findings reveal distinct molecular circuits underlying AIN pathogenesis and identify potential therapeutic targets for improving clinical management and preventing progression to chronic kidney disease.

immunology↗

bioRxiv2022

Environmental microbes promote phenotypic plasticity in Drosophila reproduction and sleep behavior

The microbiome has been hypothesized as a driving force of phenotypic variation in host organisms that is capable of extending metabolic processes, altering development, and in some cases, conferring novel functions that are critical for survival (1-5). Only a few studies have directly shown a causal role for the environmental microbiome in altering host phenotypic features. To directly assess the extent to which environmental microbes induce variation in host life history traits and behavior, we inoculated axenic Drosophila with microbes isolated from two different field sites and generated two populations with distinct bacterial and fungal profiles. We show that microbes isolated from environmental sites with modest abiotic differences induce large variation in host reproduction, fatty acid levels, stress tolerance, and sleep behavior. Importantly, clearing microbes from each experimental population removed the phenotypic differences. The results support the causal role of environmental microbes as drivers of host phenotypic variation and potentially, rapid adaptation and evolution.

physiology↗