The transcriptome of MHV-infected RAW264.7 cells offers an alternative model for macrophage innate immunity research

Yun Liu , Ting-Ting Feng , Wei Tong , Zhi Guo , Xia Li , Qi Kong , Zhi-Guang Xiang

Animal Models and Experimental Medicine ›› 2025, Vol. 8 ›› Issue (1) : 57 -66.

PDF (3913KB)
Animal Models and Experimental Medicine ›› 2025, Vol. 8 ›› Issue (1) : 57 -66. DOI: 10.1002/ame2.12443
SHORT COMMUNICATION

The transcriptome of MHV-infected RAW264.7 cells offers an alternative model for macrophage innate immunity research

Author information +
History +
PDF (3913KB)

Abstract

Background: Macrophages are the primary innate immune cells encountered by the invading coronaviruses, and their abilities to initiate inflammatory reactions, to maintain the immunity homeostasis by differential polarization, to train the innate immune system by epigenic modification have been reported in laboratory animal research.

Methods: In the current in vitro research, murine macrophage RAW 264.7 cell were infected by mouse hepatitis virus, a coronavirus existed in mouse. At 3-, 6-, 12-, 24-, and 48-h post infection (hpi.), the attached cells were washed with PBS and harvested in Trizol reagent. Then The harvest is subjected to transcriptome sequencing.

Results: The transcriptome analysis showed the immediate (3 hpi.) up regulation of DEGs related to inflammation, like Il1b and Il6. DEGs related to M2 differential polarization, like Irf4 showed up regulation at 24 hpi., the late term after viral infection. In addition, DEGs related to metabolism and histone modification, like Ezh2 were detected, which might correlate with the trained immunity of macrophages.

Conclusions: The current in vitro viral infection study showed the key innated immunity character of macrophages, which suggested the replacement value of viral infection cells model, to reduce the animal usage in preclinical research.

Keywords

coronavirus / innate immunity / macrophage / transcriptome

Cite this article

Download citation ▾
Yun Liu, Ting-Ting Feng, Wei Tong, Zhi Guo, Xia Li, Qi Kong, Zhi-Guang Xiang. The transcriptome of MHV-infected RAW264.7 cells offers an alternative model for macrophage innate immunity research. Animal Models and Experimental Medicine, 2025, 8(1): 57-66 DOI:10.1002/ame2.12443

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Cui J, Li F, Shi Z-L. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol. 2019;17:181-192.

[2]

Wu JT, Leung K, Leung GM. Nowting and foreting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study. Lancet. 2020;395:689-697.

[3]

Fan C, Wu Y, Rui X, et al. Animal models for COVID-19:advances, gaps and perspectives. Signal Transduct Target Ther. 2022;7:220.

[4]

Wynn TA, Chawla A, Pollard JW. Origins and hallmarks of macrophages: development, homeostasis, and disease. Nature. 2013;496:445-455.

[5]

Chu Z, Sun C, Sun L, et al. Primed macrophages directly and specifically reject allografts. Cell Mol Immunol. 2020;17:237-246.

[6]

Ivashkiv LB. Inflammatory signaling in macrophages: transitions from acute to tolerant and alternative activation states. Eur J Immunol. 2011;41:2477-2481.

[7]

Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008;8:958-969.

[8]

Jeyanathan M, Vaseghi-Shanjani M, Afkhami S, et al. Parenteral BCG vaccine induces lung-resident memory macrophages and trained immunity via the gut-lung axis. Nat Immunol. 2022;23:1687-1702.

[9]

Ortiz Peña N, Cherukula K, Even B, et al. Resolution of MoS2 nanosheets-induced pulmonary inflammation driven by nanoscale intracellular transformation and extracellular-vesicle shuttles. Adv Mater. 2023;35:e2305230.

[10]

Jaroonwitchawan T, Arimochi H, Sasaki Y, et al. Stimulation of the farnesoid X receptor promotes M2 macrophage polarization. Front Immunol. 2023;14:1065790.

[11]

Huangfu N, Zheng W, Xu Z, et al. RBM4 regulates M1 macrophages polarization through targeting STAT1-mediated glycolysis. Int Immunopharmacol. 2020;83:106432.

[12]

Drummer C, Saaoud F, Shao Y, et al. Trained immunity and reactivity of macrophages and endothelial cells. Arterioscler Thromb Vasc Biol. 2021;41:1032-1046.

[13]

Keating ST, Groh L, Thiem K, et al. Rewiring of glucose metabolism defines trained immunity induced by oxidized low-density lipoprotein. J Mol Med Berl Ger. 2020;98:819-831.

[14]

Zhang J, Muri J, Fitzgerald G, et al. Endothelial lactate controls muscle regeneration from ischemia by inducing M2-like macrophage polarization. Cell Metab. 2020;31:1136-1153.e7.

[15]

Davidson EJ, Yang IV. Role of epigenetics in the development of childhood asthma. Curr Opin Allergy Clin Immunol. 2018;18:132-138.

[16]

Chen S, Yang J, Wei Y, Wei X. Epigenetic regulation of macrophages: from homeostasis maintenance to host defense. Cell Mol Immunol. 2020;17:36-49.

[17]

Homberger FR. Enterotropic mouse hepatitis virus. Lab Anim. 1997;31:97-115.

[18]

Haring J, Perlman S. Mouse hepatitis virus. Curr Opin Microbiol. 2001;4:462-466.

[19]

Durand M, Troyanov Y, Laflamme P, Gregoire G. Macrophage activation syndrome treated with anakinra. J Rheumatol. 2010;37:879-880.

[20]

Teachey DT, Rheingold SR, Maude SL, et al. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood. 2013;121:5154-5157.

[21]

van der Stegen SJC, Davies DM, Wilkie S, et al. Preclinical in vivo modeling of cytokine release syndrome induced by ErbB-retargeted human T cells: identifying a window of therapeutic opportunity? J Immunol. 2013;191:4589-4598.

[22]

Kang S, Tanaka T, Narazaki M, Kishimoto T. Targeting Interleukin-6 signaling in clinic. Immunity. 2019;50:1007-1023.

[23]

Fajgenbaum DC, June CH. Cytokine Storm. N Engl J Med. 2020;383:2255-2273.

[24]

McGonagle D, Sharif K, O’Regan A, Bridgewood C. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev. 2020;19:102537.

[25]

Netea MG, Domínguez-Andrés J, Barreiro LB, et al. Defining trained immunity and its role in health and disease. Nat Rev Immunol. 2020;20:375-388.

[26]

Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324:1029-1033.

[27]

Kleinnijenhuis J, Quintin J, Preijers F, et al. BCG-induced trained immunity in NK cells: role for non-specific protection to infection. Clin Immunol. 2014;155:213-219.

[28]

Jha AK, Huang SCC, Sergushichev A, et al. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity. 2015;42:419-430.

[29]

Donnelly RP, Finlay DK. Glucose, glycolysis and lymphocyte responses. Mol Immunol. 2015;68:513-519.

[30]

Alsalman A, Al-Mterin MA, Elkord E. Role of T regulatory cells and myeloid-derived suppressor cells in COVID-19. J Immunol Res. 2022;2022:1-13.

[31]

Bain CC, Rossi AG, Lu CD. Pulmonary macrophages and SARS-Cov2 infection. Int Rev Cell Mol Biol. 2022;367:1-28.

[32]

Gibbings SL, Thomas SM, Atif SM, et al. Three unique interstitial macrophages in the murine lung at steady state. Am J Respir Cell Mol Biol. 2017;57:66-76.

[33]

Lavin Y, Winter D, Blecher-Gonen R, et al. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell. 2014;159:1312-1326.

RIGHTS & PERMISSIONS

2024 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.

AI Summary AI Mindmap
PDF (3913KB)

198

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/