JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

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

Author(s): Wei ZHANG, Bello Babatunde KAZEEM, Haitao YANG, Gang LIU, Guanglu WANG, Zhixing LI, Tao GUO, Panpan ZHAO, Jingquan DONG
Affiliation(s): Key Jiangsu Institute of Marine Resources Development, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Jiangsu Ocean University, Lianyungang 222005, China; more
Corresponding email(s): zhaopp19@mails.jlu.edu.cn, 2018000029@jou.edu.cn
Key Words: Aeromonas sobria; MAPK; NF-κB p65; Proinflammatory cytokines; Immune response

Share this article to： More <<< Previous Paper \|

Wei ZHANG, Bello Babatunde KAZEEM, Haitao YANG, Gang LIU, Guanglu WANG, Zhixing LI, Tao GUO, Panpan ZHAO, Jingquan DONG. Aeromonas sobria regulates proinflammatory immune response in mouse macrophages via activating the MAPK, AKT, and NF-κB pathways[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2100456

@article{title="Aeromonas sobria regulates proinflammatory immune response in mouse macrophages via activating the MAPK, AKT, and NF-κB pathways",
author="Wei ZHANG, Bello Babatunde KAZEEM, Haitao YANG, Gang LIU, Guanglu WANG, Zhixing LI, Tao GUO, Panpan ZHAO, Jingquan DONG",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2100456"
}

%0 Journal Article
%T Aeromonas sobria regulates proinflammatory immune response in mouse macrophages via activating the MAPK, AKT, and NF-κB pathways
%A Wei ZHANG
%A Bello Babatunde KAZEEM
%A Haitao YANG
%A Gang LIU
%A Guanglu WANG
%A Zhixing LI
%A Tao GUO
%A Panpan ZHAO
%A Jingquan DONG
%J Journal of Zhejiang University SCIENCE B
%P 782-790
%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B2100456"

TY - JOUR
T1 - Aeromonas sobria regulates proinflammatory immune response in mouse macrophages via activating the MAPK, AKT, and NF-κB pathways
A1 - Wei ZHANG
A1 - Bello Babatunde KAZEEM
A1 - Haitao YANG
A1 - Gang LIU
A1 - Guanglu WANG
A1 - Zhixing LI
A1 - Tao GUO
A1 - Panpan ZHAO
A1 - Jingquan DONG
J0 - Journal of Zhejiang University Science B
SP - 782
EP - 790
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
ER -
doi="https://doi.org/10.1631/jzus.B2100456"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Aeromonas sobria, a Gram-negative bacterium that can colonize both humans and animals, is found in a variety of environments, including water, seafood, meat, and vegetables (Cahill, 1990; Galindo et al., 2004; Song et al., 2019). Aeromonas spp. are conditionally pathogenic bacteria in aquaculture, which can rapidly proliferate, causing disease and even death in fish, especially when the environment is degraded (Neamat-Allah et al., 2020, 2021a, 2021b). In developing countries, Aeromonas spp. have been associated with a wide spectrum of infections in humans, including gastroenteritis, wound infections, septicemia, and lung infections (San Joaquin and Pickett, 1988; Wang et al., 2009; Su et al., 2013). Infections caused by Aeromonas spp. are usually more severe in immunocompromised individuals (Miyamoto et al., 2017). The presence of a plasmid encoding a β‍-lactamase in A. sobria that confers resistance to β-lactam antibiotics poses a huge challenge to the treatment of diseases caused by this microorganism (Lim and Hong, 2020). Consequently, an in-depth understanding of the interaction between A. sobria and its hosts is urgently required to enable the development of effective strategies for the treatment of A. sobria infections.

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

目的：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。
创新点：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。
方法：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。
结论：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p38MAPK、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，p38MAPK、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。

关键词组：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）

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]AdelajaA, HoffmannA, 2019. Signaling crosstalk mechanisms that may fine-tune pathogen-responsive NF-‍κB. Front Immunol, 10:433.

[2]AshallL, HortonCA, NelsonDE, et al., 2009. Pulsatile stimulation determines timing and specificity of NF-κB-dependent transcription. Science, 324(5924):242-246.

[3]CahillMM, 1990. Bacterial flora of fishes: a review. Microb Ecol, 19(1):21-41.

[4]FiguerasMJ, HornemanAJ, Martinez-MurciaA, 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.

[5]FrankeTF, YangSI, ChanTO, 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.

[6]FrankeTF, KaplanDR, CantleyLC, 1997. PI3K: downstream AKTion blocks apoptosis. Cell, 88(4):435-437.

[7]FukaoT, TanabeM, TerauchiY, et al., 2002. PI3K-mediated negative feedback regulation of IL-12 production in DCs. Nat Immunol, 3(9):875-881.

[8]GalindoCL, FadlAA, ShaJ, 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.

[9]GarringtonTP, JohnsonGL, 1999. Organization and regulation of mitogen-activated protein kinase signaling pathways. Curr Opin Cell Biol, 11(2):211-218.

[10]KirkSG, SamavatiL, LiuYS, 2020. MAP kinase phosphatase-1, a gatekeeper of the acute innate immune response. Life Sci, 241:117157.

[11]LawrenceT, GilroyDW, Colville-NashPR, et al., 2001. Possible new role for NF-‍κB in the resolution of inflammation. Nat Med, 7(12):1291-1297.

[12]LeeYG, LeeJ, ByeonSE, et al., 2011. Functional role of Akt in macrophage-mediated innate immunity. Front Biosci, 16(2):517-530.

[13]LewisTS, ShapiroPS, AhnNG, 1998. Signal transduction through MAP kinase cascades. Adv Cancer Res, 74:49-139.

[14]LimJ, HongS, 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.

[15]MartinsLM, MarquezRF, YanoT, 2002. Incidence of toxic Aeromonas isolated from food and human infection. FEMS Immunol Med Microbiol, 32(3):237-242.

[16]McCoyAJ, KoizumiY, HigaN, 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.

[17]MiyamotoY, UdakaK, SekimotoE, et al., 2017. Hematopoietic neoplasms accompanied by severe enterocolitis due to Aeromonas species. Rinsho Ketsueki, 58(4):303-308.

[18]MorrisonDK, 2012. MAP kinase pathways. Cold Spring Harb Perspect Biol, 4(11):a011254.

[19]Neamat-AllahANF, El HakimYA, MahmoudEA, 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.

[20]Neamat-AllahANF, MahmoudEA, MahsoubY, 2021a. Effects of dietary white mulberry leaves on hemato-biochemical alterations, immunosuppression and oxidative stress induced by Aeromonas hydrophila in Oreochromis niloticus. Fish Shellfish Immun, 108:147-156.

[21]Neamat-AllahANF, MahsoubYH, MahmoubEA, 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.

[22]ParkerJL, ShawJG, 2011. Aeromonas spp. clinical microbiology and disease. J Infect, 62(2):109-118.

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

[24]San JoaquinVH, PickettDA, 1988. Aeromonas-associated gatroenteritis in children. Pediatr Infect Dis J, 7(1):53-57.

[25]SongPA, DengJ, HouT, et al., 2019. Aeromonas sobria peritonitis in a peritoneal dialysis (PD) patient: a case report and review of the literature. BMC Nephrol, 20:180.

[26]SuSY, LaiCC, ChaoCM, 2013. Skin and soft-tissue infections caused by Aeromonas sobria. Intern Med, 52(8):937.

[27]WangJH, WangCY, ChiCY, 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.

[28]WangWW, TanSX, LuoJ, 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.

[29]WangXC, GongPT, ZhangN, et al., 2019. Inflammasome activation restrains the intracellular Neospora caninum proliferation in bovine macrophages. Vet Parasitol, 268:16-20.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

- Go to

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

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference