https://doi.org/doi:10.1038/s41467-026-70629-3
https://pubmed.ncbi.nlm.nih.gov/41826316/
#DrosophilaMelanogaster
#Drosophila #Immunity
Ascites is a life-threatening complication of advanced malignancies, yet how tumors disrupt systemic fluid homeostasis remains poorly understood. Here, using a Drosophila tumor allograft model that recapitulates key features of cancer-associated ascites, we identify a tumor-microbiome-renal axis that controls host fluid balance. Tumor-bearing hosts develop severe abdominal fluid accumulation accompanied by marked expansion and systemic dissemination of the gut commensal Acetobacter aceti. Tumor-induced bacterial dissemination activates innate immune signaling in the Malpighian tubules, the insect renal tubules, leading to uric acid accumulation, nephrolithiasis, and progressive ascites. Selective elimination of A. aceti, or renal-tubule-specific suppression of IMD/NF-kB signaling, abolishes these pathological changes. Conversely, mono-association of axenic hosts with A. aceti is sufficient to recapitulate the ascites phenotype through IMD pathway activation. Together, these findings demonstrate that tumors can remotely induce nephrogenic pathology through species-specific microbiome-dependent immune activation, establishing a mechanistic link between cancer progression and systemic fluid imbalance. ### Competing Interest Statement The authors have declared no competing interest. NIH Common Fund, https://ror.org/001d55x84, R01GM072562, R01CA227789 Ladies Leukemia League, N/A

Author summary The innate immune system must strike a delicate balance between effective pathogen elimination and preventing excessive inflammation. How the molecular mechanism by which this balance is achieved remains incompletely understood. Here, we uncover an unprecedented temporal feedback mechanism in Drosophila that fine-tunes immune responses against Gram-positive bacteria. This feedback loop involves a dynamic interplay among the NF-ÎşB transcription factor (Dif), the long non-coding RNA (lncRNA-CR42715), and the microRNA (miR-965-3p). We found that upon bacterial infection, Dif activates the expression of CR42715, which then functions as a molecular sponge to sequester miR-965-3p, thereby relieving its suppression on Dif mRNA. This creates a feedforward loop that amplifies early immune signaling while temporally maintaining prolonged activation through delayed miR-965-3p upregulation. Intriguingly, the expression of these components is timed. CR42715 acts early to boost immunity, while miR-965-3p increases later to dampen the immune response. This temporal feedback loop thus acts as a rheostat to ensure an effective yet self-limiting immune response. Overall, our findings reveal a previously unknown layer of regulation in a fundamental immune pathway, with potential implications for understanding similar control mechanisms in more complex organisms, including humans.

0 likes, 0 comments - drhowardsmithreports on March 10, 2026: "Nasal Spray Turbocharges Immunity A multipurpose vaccine in a nasal spray could someday protect against life-threatening viruses including flu, pneumonia, even CoVid as well as multiple allergies. It works by boosting your lungs’ immune defenses rather than targeting a specific virus or allergen. That’s a fascinating development from microbiologists and immunologists at Stanford Medicine, published in the journal Science. Instead of chasing constantly mutating viruses, this approach “trains” the immune system to stay on high alert for months. The study was conducted in mice, not humans. In experimental groups receiving the nasal vaccine—up to three doses spaced one week apart—animals are protected from viruses for at least three months, with viral levels reduced by about 700-fold. All vaccinated mice survive infection, with minimal weight loss and minimal lung inflammation. In contrast, unvaccinated control mice develop severe illness, significant weight loss, high viral loads, and often die. Besides working against viruses, the vaccine also protects against bacterial infections like Staphylococcus aureus and, wait for it, reduces allergic airway inflammation. So its an allergy medicine too. For the average person, this research suggests a future where one nasal spray could potentially replace multiple seasonal vaccines and provide rapid protection against new respiratory threats. However, this is still early-stage animal research, and human trials are just beginning. If successful, the approach could simplify vaccination and improve pandemic preparedness—but it’s not available yet. https://med.stanford.edu/news/all-news/2026/02/universal-vaccine.html https://www.sciencedaily.com/releases/2026/02/260222092258.htm #viruses #allergen #immunity #nasalspray".
Immune-microbiome coordination defines interferon setpoints in healthy humans.
Gut #microbiome & immune traits co-vary in healthy people, with stable interferon responses shaping long-term individual differences.
https://davidojcius.blogspot.com/2026/03/immune-microbiome-coordination-defines.html