UPEC kidney infection triggers neuro-immune communication leading to modulation of local renal inflammation by splenic IFN[gamma]

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 Escheri...

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Bibliographic Details
Published in:PLoS pathogens 2021-05, Vol.17 (5)
Main Authors: Steiner, Svava E, Choong, Ferdinand X, Antypas, Haris, Morado-Urbina, Carlos E, Schulz, Anette, Bersellini Farinotti, Alex, Bas, Duygu B, Svensson, Camilla I, Richter-Dahlfors, Agneta, Melican, Keira
Format: Article
Language:English
Subjects:
Care and treatment
Development and progression
Escherichia coli infections
Genetic aspects
Health aspects
Immune response
Interferon
Urologic diseases
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Summary: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 IFN[gamma] 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 [alpha]-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 IFN[gamma] in the marginal zones of the spleen that led to increasing concentrations of IFN[gamma] in the circulation. We found that IFN[gamma] 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.
ISSN:1553-7366
1553-7374
DOI:10.1371/journal.ppat.1009553