Abstract
The gut microbiota is a complex group of microorganisms that is not only closely related to intestinal immunity but also affects the whole immune system of the body. Antimicrobial peptides and reactive oxygen species participate in the regulation of gut microbiota homeostasis in invertebrates. However, it is unclear whether nitric oxide, as a key mediator of immunity that plays important roles in antipathogen activity and immune regulation, participates in the regulation of gut microbiota homeostasis. In this study, we identified a nitric oxide synthase responsible for NO production in the shrimp Marsupenaeus japonicus. The expression of Nos and the NO concentration in the gastrointestinal tract were increased significantly in shrimp orally infected with Vibrio anguillarum. After RNA interference of Nos or treatment with an inhibitor of NOS, L-NMMA, NO production decreased and the gut bacterial load increased significantly in shrimp. Treatment with the NO donor, sodium nitroprusside, increased the NO level and reduced the bacterial load significantly in the shrimp gastrointestinal tract. Mechanistically, V. anguillarum infection increased NO level via upregulation of NOS and induced phosphorylation of ERK. The activated ERK phosphorylated the NF-κB-like transcription factor, dorsal, and caused nuclear translocation of dorsal to increase expression of antimicrobial peptides (AMPs) responsible for bacterial clearance. In summary, as a signaling molecule, NOS-produced NO regulates intestinal microbiota homeostasis by promoting AMP expression against infected pathogens via the ERK-dorsal pathway in shrimp.
Highlights
Invertebrates lack adaptive immunity; they resist pathogens primarily via innate immunity, including cellular and humoral immunity
Phylogenetic analysis showed that the shrimp nitric oxide synthase (NOS) was clustered with invertebrate NOS, which are distinct from vertebrate constitutive NOS (cNOS) and iNOS (Supplementary Figure S1)
These results suggested that NOS might be involved in antibacterial immunity in the gastrointestinal tract of shrimp
Summary
Invertebrates lack adaptive immunity; they resist pathogens primarily via innate immunity, including cellular and humoral immunity. Several immune effectors against pathogens have been identified in invertebrates, such as antimicrobial peptides (AMPs), melanin, and reactive oxygen species [1, 2]. A highly reactive and unstable freeradical gas, nitric oxide (NO) has been discovered as another effector in response to pathogen infection in several species of invertebrates [3]. NNOS and eNOS are recognized to have a wider cell and tissue distribution, and to be regulated by cytokines, microbial products, and hormones [9]. To date, only a single NOS has been found in each invertebrate species, which has constitutive and/or inducible characteristics [11, 12]. A NOS has been identified in shrimp, Marsupenaeus japonicus [13], but its property and function need to be clarified
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