Nutrient sensing signaling functions as the sensor and regulator of immunometabolic changes in grass carp during Flavobacterium columnare infection

In order to illustrate the immunometabolic changes of fish during bacterial infection, grass carp (Ctenopharyngodon idellus) was injected with Flavobacterium columnare (F. columnare) and then the immune response, nutrient metabolism and related signaling pathways were assayed from 6 h post injection (hpi) to 7 days post injection (dpi). After F. columnare injection, gill lamellae showed obvious fusion and higher mRNA expression levels of pro-inflammatory cytokines. The mRNA expression levels of TNF-alpha, IL-1 beta and IL-8 in the head kidney were also significantly upregulated at 6 hpi and 3 dpi. Moreover, the expression of IgZ in the gill was significantly upregulated at 3 dpi and 7 dpi, while the expression of IgM in the head kidney was significantly upregulated at 1 dpi and 3 dpi after F. columnare injection. During bacterial infection, the systematic nutrient metabolism was also significantly affected. Hepatic glycolysis, indicated by GK mRNA expression and PK activity, was significantly upregulated at 1 dpi, while glucogenesis, indicated by PEPCK mRNA expression and enzyme activity, was significantly increased at later time, which resulted in the decreased hepatic glycogen content at ldpi but increased glycogen content at 7 dpi in the experimental group. LPL, which catalyzed the lipid catabolism, showed decreased mRNA expression and enzyme activity at 6 hpi, while ACC, which was rate-limiting of FA synthesis, was significantly increased at 6 hpi, 3 dpi and 7 dpi. During this process, the nutrient sensing signaling was also significantly affected. TOR signaling in grass carp was significantly activated while ERK signaling was significantly inhibited after F. columnare infection, both of which might function as the sensor and regulator of fish immunometabolic changes.