UPEC kidney infection triggers neuro-immune communication leading to modulation of local renal inflammation by splenic IFNγ
| العنوان: | UPEC kidney infection triggers neuro-immune communication leading to modulation of local renal inflammation by splenic IFNγ |
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| المؤلفون: | Steiner, Svava E., Choong, F. X., Antypas, Haris, Morado-Urbina, C. E., Schulz, Anette, Farinotti, Alex Bersellini, Bas, Duygu B., Svensson, Camilla I., Richter-Dahlfors, Agneta, Melican, Keira |
| المصدر: | PLoS Pathogens. 17(5) |
| مصطلحات موضوعية: | alpha hemolysin, gamma interferon, interleukin 1beta, interleukin 6, interleukin 8, A-498 cell line, Article, basement membrane, controlled study, enzyme linked immunosorbent assay, epithelium cell, fluorescence microscopy, gene expression, host pathogen interaction, human, human cell, in vivo study, kidney infection, kidney tubule, sensory nerve cell, spleen, uropathogenic Escherichia coli, animal, complication, Escherichia coli infection, immunomodulation, inflammation, kidney, male, metabolism, microbiology, pathology, physiology, rat, Sprague Dawley rat, Animals, Epithelial Cells, Escherichia coli Infections, Host-Pathogen Interactions, Interferon-gamma, Neuroimmunomodulation, Rats, Sprague-Dawley |
| الوصف: | Bacterial infection results in a veritable cascade of host responses, both local and systemic. To study the initial stages of host-pathogen interaction in living tissue we use spatially-temporally controlled in vivo models. Using this approach, we show here that within 4 h of a uropathogenic Escherichia coli (UPEC) infection in the kidney, an IFNγ response is triggered in the spleen. This rapid infection-mediated inter-organ communication was found to be transmitted via nerve signalling. Bacterial expression of the toxin α-hemolysin directly and indirectly activated sensory neurons, which were identified in the basement membrane of renal tubules. Nerve activation was transmitted via the splenic nerve, inducing upregulation of IFNγ in the marginal zones of the spleen that led to increasing concentrations of IFNγ in the circulation. We found that IFNγ modulated the inflammatory signalling generated by renal epithelia cells in response to UPEC infection. This demonstrates a new concept in the host response to kidney infection; the role of nerves in sensing infection and rapidly triggering a systemic response which can modulate inflammation at the site of infection. The interplay between the nervous and immune systems is an exciting, developing field with the appealing prospect of non-pharmaceutical interventions. Our study identifies an important role for systemic neuro-immune communication in modulating inflammation during the very first hours of a local bacterial infection in vivo. |
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| الوصول الحر: | https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-309639Test https://doi.org/10.1371/journal.ppat.1009553Test |
| قاعدة البيانات: | SwePub |
| تدمد: | 15537366 15537374 |
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| DOI: | 10.1371/journal.ppat.1009553 |