Akt1/mTORC1 signaling modulates adaptive immune response of Nile tilapia by promoting lymphocyte activation and proliferation

• Published in: Developmental and comparative immunology 2021-06, Vol.119, p.104042-104042, Article 104042
• Main Authors: Ai, Kete, Yan, Jie, Li, Kang, Li, Cheng, Zhang, Yu, Liang, Wei, Li, Jiaqi, Wei, Xiumei, Yang, Jialong
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Adaptive Immunity - genetics; Adaptive Immunity - immunology; Adaptive systems; Aeromonas hydrophila - immunology; Aeromonas hydrophila - physiology; Akt1; AKT1 protein; Amino Acid Sequence; Animals; CD122 antigen; CD44 antigen; Cell activation; Cell cycle; Cell Proliferation - genetics; Cell survival; Cichlids - genetics; Cichlids - immunology; Cichlids - microbiology; Conserved sequence; Evolution; Fish Diseases - genetics; Fish Diseases - immunology; Fish Diseases - microbiology; Fish Proteins - genetics; Fish Proteins - immunology; Fish Proteins - metabolism; Host-Pathogen Interactions - immunology; Immune response; Immune system; Immunity; Kinases; Lymphocyte activation; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Mechanistic Target of Rapamycin Complex 1 - chemistry; Mechanistic Target of Rapamycin Complex 1 - genetics; Mechanistic Target of Rapamycin Complex 1 - immunology; Metabolism; Models, Molecular; Oreochromis niloticus; Organs; Phosphorylation; Phylogeny; Ponds; Proliferation; Protein Conformation; Protein kinase; Proto-Oncogene Proteins c-akt - classification; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - immunology; Regulatory mechanisms (biology); Regulatory sequences; Sequence Homology, Amino Acid; Signal Transduction - genetics; Signal Transduction - immunology; Signaling; Spleen; Threonine; Tilapia; Transcription; Transcriptome - immunology; Vertebrates; γ-Interferon
• ISSN: 0145-305X; 1879-0089
• DOI: 10.1016/j.dci.2021.104042

Serving as a significant signaling molecule, RAC-alpha serine/threonine-protein kinase (Akt1) plays indispensable roles in cell cycle, growth, survival, metabolism, as well as immune response. However, how Akt1 regulates adaptive immune response in early vertebrate, especially the teleost, is largely unknown. Here, using a Nile tilapia Oreochromis niloticus model, we investigated the regulatory role of Akt1 in adaptive immunity of teleost. Both sequence and structure of the O. niloticus Akt1 (OnAkt1), were evolutionarily conserved comparing with the counterparts from other vertebrates. mRNA of OnAkt1 was widely expressed in lymphoid organs/tissues of Nile tilapia, with relative higher level in PBL. After Nile tilapia was infected by Aeromonas hydrophila, both transcription and phosphorylation levels of OnAkt1 were obviously elevated in spleen lymphocytes at the adaptive immune stage, suggesting Akt1 participated in primary adaptive immune response of Nile tilapia. Furthermore, OnAkt1 transcript or phosphorylation was dramatically augmented after spleen lymphocytes were activated by T cell specific mitogen PHA or lymphocyte agonist PMA. More critically, inhibition of Akt1 by specific inhibitor crippled the activation of downstream mTORC1 signaling, and impaired the up-regulation of T cell activation markers CD44, IFN-γ and CD122 in spleen lymphocytes upon PHA-induced T cell activation. Meanwhile, blockade of Akt1-activated mTORC1 signaling also decreased the frequency of BrdU+ lymphocytes during A. hydrophila infection, indicating the critical role of Akt1 in regulating lymphocyte proliferation of Nile tilapia. Together, our results demonstrated that Akt1 modulated adaptive immune response of Nile tilapia by promoting lymphocyte activation and proliferation via mTORC1 signaling. Our study enriched the regulatory mechanism of lymphocyte-mediated adaptive immunity in teleost, and thus provided novel insights into the evolution of adaptive immune system. •The mRNA of Nile tilapia Akt1 expresses widely in lymphoid tissues.•OnAkt1 takes part in primary response of the adaptive immunity.•Akt1/mTORC1 axis regulates lymphocyte activation of Nile tilapia.•Akt1/mTORC1 signaling is essential for lymphocyte proliferation.