Exosomal miR-224 contributes to hemolymph microbiota homeostasis during bacterial infection in crustacean

• Main Authors: Gong, Yi, Wei, Xiaoyuan, Sun, Wanwei, Ren, Xin, Chen, Jiao, Aweya, Jude Juventus, Ma, Hongyu, Chan, Kok-Gan, Zhang, Yueling, Li, Shengkang
• Format: Article
• Published: Public Library of Science 2021
• Subjects: R Medicine
• Online Access: http://eprints.um.edu.my/34346/

Author summary Exosomes are small membrane vesicles of endocytic origin which are widely involved in the regulation of a variety of pathological processes in mammals. Yet, although the antibacterial function of exosomes has been discovered for many years, the relationship between exosomes and hemolymph microbiota homeostasis remains unknown. In the present study, we identified the miRNAs packaged by exosomes that were possibly involved in Vibrio parahaemolyticus infection by modulating hemolymph microbiota homeostasis in crustacean mud crab Scylla paramamosain. Moreover, it was found that miR-224 was densely packaged in exosomes after Vibrio parahaemolyticus challenge, resulting in the suppression of HSP70 and disruption of the HSP70-TRAF6 complex in recipient hemocytes, then the released TRAF6 was further interacted with Ecsit to regulate ROS and ALFs levels, which eventually affected hemolymph microbiota homeostasis to cope with pathogenic bacteria infection. Our finding is the first to reveal the relationship between exosomes and hemolymph microbiota homeostasis in animals, which shows a novel molecular mechanism of invertebrate resistance to pathogenic microbial infection. It is well known that exosomes could serve as anti-microbial immune factors in animals. However, despite growing evidences have shown that the homeostasis of the hemolymph microbiota was vital for immune regulation in crustaceans, the relationship between exosomes and hemolymph microbiota homeostasis during pathogenic bacteria infection has not been addressed. Here, we reported that exosomes released from Vibrio parahaemolyticus-infected mud crabs (Scylla paramamosain) could help to maintain the homeostasis of hemolymph microbiota and have a protective effect on the mortality of the host during the infection process. We further confirmed that miR-224 was densely packaged in these exosomes, resulting in the suppression of HSP70 and disruption of the HSP70-TRAF6 complex, then the released TRAF6 further interacted with Ecsit to regulate the production of mitochondrial ROS (mROS) and the expression of Anti-lipopolysaccharide factors (ALFs) in recipient hemocytes, which eventually affected hemolymph microbiota homeostasis in response to the pathogenic bacteria infection in mud crab. To the best of our knowledge, this is the first document that reports the role of exosome in the hemolymph microbiota homeostasis modulation during pathogen infection, which reveals the crosstalk between exosomal miRNAs and innate immune response in crustaceans.