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UPEC kidney infection triggers neuro-immune communication leading to modulation of local renal inflammation by splenic IFNγ
Authors:Svava E Steiner  Ferdinand X Choong  Haris Antypas  Carlos E Morado-Urbina  Anette Schulz  Alex Bersellini Farinotti  Duygu B Bas  Camilla I Svensson  Agneta Richter-Dahlfors  Keira Melican
Institution:1. AIMES—Center for the Advancement of Integrated Medical and Engineering Sciences, Karolinska Institutet and KTH Royal Institute of Technology, Stockholm, Sweden;2. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden;3. Department for Physiology and Pharmacology, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden;University of California, Davis, UNITED STATES
Abstract: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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