Skip to main content

Aeromonas sobria regulates proinflammatory immune response in mouse macrophages via activating the MAPK, AKT, and NF-κB pathways

MAPK、 AKT和NF-κB信号通路在温和气单胞菌诱导宿主细胞炎性应答中的作用及分子机制研究



以利用小鼠原代腹腔巨噬细胞建立了一种温和气单胞菌体外感染模型, 探究MAPK、 AKT和NF-κB信号通路在温和气单胞菌诱导宿主细胞炎性应答中的作用及相关的分子机制, 为防治温和气单胞菌造成的感染提供新的治疗靶点.


首次探究了丝裂原活化蛋白激酶(mitogen-activated protein kinase, MAPK)、 蛋白激酶B(protein kinase B, AKT)和核因子κB(nuclear factor kappa B, NF-κB)信号通路在温和气单胞菌诱导宿主细胞炎性应答中的作用及相关的分子机制, 并分别从正反向进行了研究, 围绕NF-κB、 MAPK、 磷酯酰肌醇-3-激酶(phosphatidylinositol 3 kinase, PI3K)/AKT等与炎症反应密切相关的信号通路, 探索温和气单胞菌调控宿主细胞免疫应答的作用机制, 为防治温和气单胞菌感染的治疗提供新的靶点.


本研究利用小鼠原代腹腔巨噬细胞建立了一种温和气单胞菌体外感染模型, 通过测定感染细胞培养上清中的炎性细胞因子分泌水平, 初步确定其可引起小鼠原代腹腔巨噬细胞产生炎性应答. 应用荧光定量PCR、 蛋白质免疫印迹、 阻断实验、 酶联免疫吸附试验和免疫荧光等技术, 围绕NF-κB、 MAPK、 PI3K/AKT等与炎症反应密切相关的信号通路, 探索温和气单胞菌调控宿主细胞免疫应答的作用机制, 为防治温和气单胞菌感染的治疗提供新的靶点.


温和气单胞菌体外刺激小鼠腹腔巨噬细胞可以引起多种炎性细胞因子分泌水平的升高, 如白细胞介素1β(interleukin-1β, IL-1β)、 白细胞介素6(interleukin-6, IL-6)、 白细胞介素12(interleukin-12, IL-12)和肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α). 同时温和气单胞菌可以通过p38 MAPK、 c-Jun氨基末端激酶(c-Jun N-terminal kinase, JNK)/MAPK及NF-κB信号通路调节小鼠腹腔巨噬细胞促炎性因子的转录和表达, 并通过AKT信号通路负调节促炎性因子的转录和表达等. 因此, p38 MAPK、 JNK/MAPK和NF-κB信号通路均可作为潜在的药物干预靶点治疗温和气单胞菌引起的各类炎症感染.

This is a preview of subscription content, access via your institution.


  1. Adelaja A, Hoffmann A, 2019. Signaling crosstalk mechanisms that may fine-tune pathogen-responsive NF-κB. Front Immunol, 10:433.

    CAS  Article  Google Scholar 

  2. Ashall L, Horton CA, Nelson DE, et al., 2009. Pulsatile stimulation determines timing and specificity of NF-κB-dependent transcription. Science, 324(5924):242–246.

    CAS  Article  Google Scholar 

  3. Cahill MM, 1990. Bacterial flora of fishes: a review. Microb Ecol, 19(1):21–41.

    CAS  Article  Google Scholar 

  4. Figueras MJ, Horneman AJ, Martinez-Murcia A, et al., 2007. Controversial data on the association of Aeromonas with diarrhoea in a recent Hong Kong study. J Med Microbiol, 56(7):996–998.

    CAS  Article  Google Scholar 

  5. Franke TF, Yang SI, Chan TO, et al., 1995. The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell, 81(5):727–736.

    CAS  Article  Google Scholar 

  6. Franke TF, Kaplan DR, Cantley LC, 1997. PI3K: downstream AKTion blocks apoptosis. Cell, 88(4):435–437.

    CAS  Article  Google Scholar 

  7. Fukao T, Tanabe M, Terauchi Y, et al., 2002. PI3K-mediated negative feedback regulation of IL-12 production in DCs. Nat Immunol, 3(9):875–881.

    CAS  Article  Google Scholar 

  8. Galindo CL, Fadl AA, Sha J, et al., 2004. Aeromonas hydrophila cytotoxic enterotoxin activates mitogen-activated protein kinases and induces apoptosis in murine macrophages and human intestinal epithelial cells. J Biol Chem, 279(36):37597–37612.

    CAS  Article  Google Scholar 

  9. Garrington TP, Johnson GL, 1999. Organization and regulation of mitogen-activated protein kinase signaling pathways. Curr Opin Cell Biol, 11(2):211–218.

    CAS  Article  Google Scholar 

  10. Kirk SG, Samavati L, Liu YS, 2020. MAP kinase phosphatase-1, a gatekeeper of the acute innate immune response. Life Sci, 241:117157.

    CAS  Article  Google Scholar 

  11. Lawrence T, Gilroy DW, Colville-Nash PR, et al., 2001. Possible new role for NF-κB in the resolution of inflammation. Nat Med, 7(12):1291–1297.

    CAS  Article  Google Scholar 

  12. Lee YG, Lee J, Byeon SE, et al., 2011. Functional role of Akt in macrophage-mediated innate immunity. Front Biosci, 16(2):517–530.

    CAS  Article  Google Scholar 

  13. Lewis TS, Shapiro PS, Ahn NG, 1998. Signal transduction through MAP kinase cascades. Adv Cancer Res, 74:49–139.

    CAS  Article  Google Scholar 

  14. Lim J, Hong S, 2020. Characterization of Aeromonas salmonicida and A. sobria isolated from cultured salmonid fish in Korea and development of a vaccine against furunculosis. J Fish Dis, 43(5):609–620.

    CAS  Article  Google Scholar 

  15. Martins LM, Marquez RF, Yano T, 2002. Incidence of toxic Aeromonas isolated from food and human infection. FEMS Immunol Med Microbiol, 32(3):237–242.

    CAS  Article  Google Scholar 

  16. McCoy AJ, Koizumi Y, Higa N, et al., 2010. Differential regulation of caspase-1 activation via NLRP3/NLRC4 inflammasomes mediated by aerolysin and type III secretion system during Aeromonas veronii infection. J Immunol, 185(11):7077–7084.

    CAS  Article  Google Scholar 

  17. Miyamoto Y, Udaka K, Sekimoto E, et al., 2017. Hematopoietic neoplasms accompanied by severe enterocolitis due to Aeromonas species. Rinsho Ketsueki, 58(4):303–308.

    PubMed  Google Scholar 

  18. Morrison DK, 2012. MAP kinase pathways. Cold Spring Harb Perspect Biol, 4(11):a011254.

    Article  Google Scholar 

  19. Neamat-Allah ANF, El Hakim YA, Mahmoud EA, 2020. Alleviating effects of β-glucan in Oreochromis niloticus on growth performance, immune reactions, antioxidant, transcriptomics disorders and resistance to Aeromonas sobria caused by atrazine. Aquac Res, 51(5):1801–1812.

    CAS  Article  Google Scholar 

  20. Neamat-Allah ANF, Mahmoud EA, Mahsoub Y, 2021a. Effects of dietary white mulberry leaves on hematobiochemical alterations, immunosuppression and oxidative stress induced by Aeromonas hydrophila in Oreochromis niloticus. Fish Shellfish Immun, 108:147–156.

    CAS  Article  Google Scholar 

  21. Neamat-Allah ANF, Mahsoub YH, Mahmoub EA, 2021b. The potential benefits of dietary β-glucan against growth retardation, immunosuppression, oxidative stress and expression of related genes and susceptibility to Aeromonas hydrophila challenge in Oreochromis niloticus induced by herbicide pendimethalin. Aquac Res, 52(2):518–528.

    CAS  Article  Google Scholar 

  22. Parker JL, Shaw JG, 2011. Aeromonas spp. clinical microbiology and disease. J Infect, 62(2):109–118.

    Article  Google Scholar 

  23. Perkins ND, 2006. Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathway. Oncogene, 25(51):6717–6730.

    CAS  Article  Google Scholar 

  24. San Joaquin VH, Pickett DA, 1988. Aeromonas-associated gatroenteritis in children. Pediatr Infect Dis J, 7(1):53–57.

    CAS  Article  Google Scholar 

  25. Song PA, Deng J, Hou T, et al., 2019. Aeromonas sobria peritonitis in a peritoneal dialysis (PD) patient: a case report and review of the literature. BMC Nephrol, 20:180.

    Article  Google Scholar 

  26. Su SY, Lai CC, Chao CM, 2013. Skin and soft-tissue infections caused by Aeromonas sobria. Intern Med, 52(8):937.

    Article  Google Scholar 

  27. Wang JH, Wang CY, Chi CY, et al., 2009. Clinical presentations, prognostic factors, and mortality in patients with Aeromonas sobria complex bacteremia in a teaching hospital: a 5-year experience. J Microbiol Immunol Infect, 42(6):510–515.

    PubMed  Google Scholar 

  28. Wang WW, Tan SX, Luo J, et al., 2019. GWAS analysis indicated importance of NF-κB signaling pathway in host resistance against motile Aeromonas septicemia disease in catfish. Mar Biotechnol, 21(3):335–347.

    CAS  Article  Google Scholar 

  29. Wang XC, Gong PT, Zhang N, et al., 2019. Inflammasome activation restrains the intracellular Neospora caninum proliferation in bovine macrophages. Vet Parasitol, 268: 16–20.

    CAS  Article  Google Scholar 

Download references


This work was supported by the Open Foundation of Key Jiangsu Institute of Marine Resources Development (No. JSIMR202016) and the Jiangsu Distinguished Professor Program (No. KK19515), China. We thank Charlesworth Author Services for the English language editing.

Author information




Panpan ZHAO and Jingquan DONG conceptualized and designed the study. Wei ZHANG collected the data. Wei ZHANG, Bello Babatunde KAZEEM, Haitao YANG, Guanglu WANG, Zhixing LI, and Tao GUO performed the data processing and data analysis. Wei ZHANG, Bello Babatunde KAZEEM, and Panpan ZHAO wrote and edited the manuscript. Wei ZHANG and Bello Babatunde KAZEEM drew the figures. Jingquan DONG and Gang LIU checked the final version, and provided program finance support. All authors have read and approved the final manuscript and, therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.

Corresponding authors

Correspondence to Panpan Zhao or Jingquan Dong.

Ethics declarations

Wei ZHANG, Bello Babatunde KAZEEM, Haitao YANG, Gang LIU, Guanglu WANG, Zhixing LI, Tao GUO, Panpan ZHAO, and Jingquan DONG declare that they have no conflict of interest.

All animal experiments were strictly performed according to the guidelines for the Animal Welfare and Research Ethics Committee of Jiangsu Ocean University (Permit Number: 2017124242). All institutional and national guidelines for the care and use of laboratory animals were followed.

Additional information

Materials and methods

Detailed methods are provided in the electronic supplementary materials of this paper.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zhang, W., Kazeem, B.B., Yang, H. et al. Aeromonas sobria regulates proinflammatory immune response in mouse macrophages via activating the MAPK, AKT, and NF-κB pathways. J. Zhejiang Univ. Sci. B 22, 782–790 (2021).

Download citation


  • 温和气单胞菌
  • 免疫应答
  • 丝裂原活化蛋白激酶(MAPK)
  • 蛋白激酶B(AKT)
  • 核因子κB(NF-κB)