Citrobacter koseri stimulates dendritic cells to induce IL-33 expression via abundant ATP production

Abstract

Introduction. Food allergies (FAs) occur due to intestinal immune dysfunction elicited by dysbiotic conditions. It was previously determined by us that Citrobacter species propagate in the faeces of mice with FAs and worsen allergic symptoms by inducing the allergenic cytokine IL-33. Dendritic cells can play important roles in regulation of FA responses. Hypothesis. Citrobacter species propagating in intestines of mice worsen allergic symptoms by stimulating dendritic cells to induce IL-33 expression. Aim. The aim of the present study was to analyse whether C. koseri stimulates dendritic cells to induce IL-33 expression. Methodology. IL-33 expression was evaluated in a DC2.4 mouse dendritic cell line stimulated by live or heat-inactivated C. koseri JCM1658, ATP, LPS extracted from C. koseri JCM1658 or other enterobacteria by real-time PCR. The ATP concentration and number of live bacteria in the culture supernatant were measured simultaneously. Results. Live C. koseri JCM1658 induced higher levels of IL-33 expression than other enterobacteria tested, but such a response was not elicited by heat-inactivated C. koseri JCM1658. LPS extracted from C. koseri JCM1658 did not induce IL-33 expression and suppressed live C. koseri JCM1658-induced IL-33 expression via the activation of Toll-like receptor 4 signalling. Furthermore, ATP produced by C. koseri JCM1658 stimulated dendritic cells to induce IL-33 expression by stimulating the P2X7 receptor, and LPS attenuated extracellular ATP-induced IL-33 expression. C. koseri JCM1658 was observed to proliferate more vigorously and produce more ATP than other enterobacteria. Conclusion. C. koseri acts as an allergenic bacterium through ATP production, stimulating dendritic cells to induce IL-33 expression, while LPS released from inactivated C. koseri JCM1658 attenuates this allergenicity.

Hepatic pannexin‐1 mediates ST2+ regulatory T cells promoting resolution of inflammation in lipopolysaccharide‐induced endotoxemia

“…Consistently, Kataoka et al reported that ATP induced IL-33 expression by stimulating the P2X7 receptor under conditions of GNB infection. 68 Another study also reported that the P2X7 receptor was involved in IL-33 production by increasing the concentration of Ca 2+ . 62 Whether P2X7 can regulate any transcription factor that induces IL-33 expression, such as CDX2, remains unclear.…”

Multi-omics Reveal the Enabling Factors of Aplastic Anaemia

“…Citrobacter has been identi ed as a microorganism that can cause intestinal in ammation; thus, Citrobacter rodentium is inextricably linked to human immune cells, especially dendritic cells and CD4+ T cells 26 . Citrobacter koseri, a subspecies of Citrobacter, stimulates dendritic cells to induce IL-33 through massive ATP production 27 . Plasmacytoid dendritic cells (pDCs) are the main dendritic cells upregulated upon stimulation in Citrobacter rodentium infection 28 .…”

Understanding the Role of Purinergic P2X7 Receptors in the Gastrointestinal System: A Systematic Review

“…There were eleven GI infection models undertaken in mice ( Heiss et al, 2008 ; Keating et al, 2011 ; Coquenlorge et al, 2014 ; Miller et al, 2015 ; Huang et al, 2017 ; Shimokawa et al, 2017 ; Liu et al, 2018 ; Stark et al, 2018 ; Guan et al, 2021 ; Kataoka et al, 2021 ), human fetal small intestinal epithelial cells (FHs 74 Int cells) ( Quan et al, 2018 ), human liver and spleen cell samples ( Stark et al, 2018 ), human longitudinal muscle-myenteric plexus ( Coquenlorge et al, 2014 ).…”

“…Infective agents used included T. gondii ( Miller et al, 2015 ; Huang et al, 2017 ; Quan et al, 2018 ), T. spiralis ( Keating et al, 2011 ; Huang et al, 2017 ; Guan et al, 2021 ), Heligmosomoides polygyrus (Hp) ( Shimokawa et al, 2017 ), lymphocytic choriomeningitis (LCMV) ( Stark et al, 2018 ), C. difficile ( Liu et al, 2018 ), C. koseri ( Kataoka et al, 2021 ), L. monocytogenes ( Heiss et al, 2008 ), and LPS from E. coli and Salmonella typhosa ( Coquenlorge et al, 2014 ). Modes of administration included orally ( Heiss et al, 2008 ; Keating et al, 2011 ; Miller et al, 2015 ; Huang et al, 2017 ; Shimokawa et al, 2017 ; Stark et al, 2018 ) or intraperitoneally ( Stark et al, 2018 ) for in vivo murine models.…”

“…Modes of administration included orally ( Heiss et al, 2008 ; Keating et al, 2011 ; Miller et al, 2015 ; Huang et al, 2017 ; Shimokawa et al, 2017 ; Stark et al, 2018 ) or intraperitoneally ( Stark et al, 2018 ) for in vivo murine models. These studies involved P2X7R KO mice ( Heiss et al, 2008 ; Keating et al, 2011 ; Miller et al, 2015 ; Huang et al, 2017 ; Stark et al, 2018 ), pharmacological inhibition of P2X7R ( Coquenlorge et al, 2014 ; Huang et al, 2017 ; Shimokawa et al, 2017 ; Liu et al, 2018 ; Stark et al, 2018 ; Guan et al, 2021 ; Kataoka et al, 2021 ), P2X7R siRNA ( Liu et al, 2018 ; Quan et al, 2018 ), ARTC2.2-blocking nanobody s+16a ( Stark et al, 2018 ) and anti-P2X7R antibodies ( Heiss et al, 2008 ).…”