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Selenium Deficiency Aggravates Heat Stress Pneumonia in Chickens by Disrupting the M1/M2 Balance

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Abstract

Selenium (Se) is an essential trace element found in the body. Se deficiency and M1/M2 imbalance are closely related to inflammation. Heat stress can decrease immune function and cause inflammation. In order to investigate whether Se deficiency can aggravate pneumonia caused by heat stress and the role of M1/M2 imbalance in the occurrence of pneumonia, 100 AA broilers were divided into two groups and fed the conventional diet (0.2 mg/kg Se) and the Se-deficient diet (0.03 mg/kg Se). After 40 days of feeding, the normal feeding group was randomly divided into a control group and a heat stress group. At the same time, the Se-deficient diet feeding group was randomly divided into a low Se group and a low Se heat stress group, with 25 chickens in each group. The model was established by exposure at 40℃. Six hours later, broilers were euthanized, and their lung tissues were collected. Hematoxylin and eosin staining, immunofluorescence, quantitative real-time PCR, and western blotting were used to detect lung histopathological changes and the expression of M1/M2 markers, nuclear receptor-κB (NF-κB) pathway genes, and heat shock proteins. Meanwhile, the activity and content of oxidative stress-related indices were also detected. We found that the expression of interleukin-1β, interleukin-6, interleukin-12, and tumor necrosis factor-α was upregulated and the expression of interleukin-2, interleukin-10, and interferon-γ was downregulated. Immunofluorescence showed that the expression of CD16 was increased, the expression of CD163 was weakened, and the M1/M2 imbalance was present. In addition, the NF-κB pathway was activated by the increased expressions of heat shock proteins and oxidative stress. There was an increase in malondialdehyde, nitric oxide, and inducible nitric oxide synthase content, while the activity of total antioxidant capacity, glutathione peroxidase, catalase, and superoxide dismutase decreased, and the expression of NF-κB and cyclooxygenase-2 increased. These results suggest that low Se induces M1/M2 imbalance through oxidative stress activation of the NF-κB pathway and aggravates lung tissue inflammation caused by heat stress. This study offers a theoretical basis for exploring the pathogenesis of various kinds of inflammation induced by Se deficiency from the perspective of M1/M2 and provides a reference for the prevention of such diseases.

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References

  1. Huang Z et al (2012) The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal 16:705–743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Mehdi Y et al (2013) Selenium in the environment, metabolism and involvement in body functions. Molecules (Basel, Switzerland) 18:3292–3311

    Article  CAS  Google Scholar 

  3. Kieliszek M (2019) Selenium-fascinating microelement, properties and sources in food. Molecules (Basel, Switzerland) 24

  4. Huang JQ et al (2011) The selenium deficiency disease exudative diathesis in chicks is associated with downregulation of seven common selenoprotein genes in liver and muscle. J Nutr 141:1605–1610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Dalgaard TS et al (2018) The influence of selenium and selenoproteins on immune responses of poultry and pigs. Anim Feed Sci Technol 238:73–83

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chen J (2012) An original discovery: selenium deficiency and Keshan disease (an endemic heart disease). Asia Pac J Clin Nutr 21:320–326

    PubMed  Google Scholar 

  7. Moreno-Reyes R et al (2001) Kashin-Beck disease and iodine deficiency in Tibet. Int Orthop 25:164–166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Gao X et al (2016) Selenium deficiency-induced inflammation and increased expression of regulating inflammatory cytokines in the chicken gastrointestinal tract. Biol Trace Elem Res 173:210–218

    Article  CAS  PubMed  Google Scholar 

  9. Kaushal N et al (2014) Crucial role of macrophage selenoproteins in experimental colitis. J Immunol (Baltimore, Md.: 1950) 193:3683–3692

    Article  CAS  Google Scholar 

  10. Qin L et al (2020) MiR-196-5p involvement in selenium deficiency-induced immune damage via targeting of NFκBIA in the chicken trachea. Metallomics : integrated biometal science 12:1679–1692

    Article  CAS  Google Scholar 

  11. Yu J et al (2015) The role of nitric oxide and oxidative stress in intestinal damage induced by selenium deficiency in chickens. Biol Trace Elem Res 163:144–153

    Article  CAS  PubMed  Google Scholar 

  12. Youn HS et al (2008) Selenium suppresses the activation of transcription factor NF-kappa B and IRF3 induced by TLR3 or TLR4 agonists. Int Immunopharmacol 8:495–501

    Article  CAS  PubMed  Google Scholar 

  13. Zhuang C et al (2020) Selenomethionine suppressed TLR4/NF-κB pathway by activating selenoprotein S to alleviate ESBL Escherichia coli-induced inflammation in bovine mammary epithelial cells and macrophages. Front Microbiol 11:1461

    Article  PubMed  PubMed Central  Google Scholar 

  14. Safir N et al (2003) The effect of selenium on immune functions of J774.1 cells. Clin Chem Lab Med 41:1005–1011

    Article  CAS  PubMed  Google Scholar 

  15. Cheng P et al (2021) Macrophages in lung injury, repair, and fibrosis. Cells 10

  16. Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3:23–35

    Article  CAS  PubMed  Google Scholar 

  17. Sica A, Mantovani A (2012) Macrophage plasticity and polarization: in vivo veritas. J Clin Investig 122:787–795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chawla A (2010) Control of macrophage activation and function by PPARs. Circ Res 106:1559–1569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wang N et al (2014) Molecular mechanisms that influence the macrophage m1–m2 polarization balance. Front Immunol 5:614

    Article  PubMed  PubMed Central  Google Scholar 

  20. Martinez FO et al (2009) Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol 27:451–483

    Article  CAS  PubMed  Google Scholar 

  21. Escribese MM et al (2012) Influence of low oxygen tensions on macrophage polarization. Immunobiology 217:1233–1240

    Article  CAS  PubMed  Google Scholar 

  22. Mouton AJ et al (2020) Obesity, hypertension, and cardiac dysfunction: novel roles of immunometabolism in macrophage activation and inflammation. Circ Res 126:789–806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kanter JE et al (2012) Diabetes promotes an inflammatory macrophage phenotype and atherosclerosis through acyl-CoA synthetase 1. Proc Natl Acad Sci USA 109:E715-724

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Agoro R et al (2018) Cell iron status influences macrophage polarization. PloS One 13:e0196921

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Draijer C et al (2013) Characterization of macrophage phenotypes in three murine models of house-dust-mite-induced asthma. Mediat Inflamm 2013:632049

    Article  CAS  Google Scholar 

  26. Lissner D et al (2015) Monocyte and M1 macrophage-induced barrier defect contributes to chronic intestinal inflammation in IBD. Inflamm Bowel Dis 21:1297–1305

    PubMed  Google Scholar 

  27. Wang Y et al (2021) Environmentally relevant concentration of sulfamethoxazole-induced oxidative stress-cascaded damages in the intestine of grass carp and the therapeutic application of exogenous lycopene. Environ Pollut (Barking, Essex: 1987) 274:116597

    Article  CAS  Google Scholar 

  28. Wang Z et al (2020) Inulin alleviates inflammation of alcoholic liver disease via SCFAs-inducing suppression of M1 and facilitation of M2 macrophages in mice. Int Immunopharmacol 78:106062

    Article  CAS  PubMed  Google Scholar 

  29. Khan AZ et al (2019) Selenium-enriched probiotics improve hepatic protection by regulating pro-inflammatory cytokines and antioxidant capacity in broilers under heat stress conditions. J Adv Vet Anim Res 6:355–361

    Article  PubMed  PubMed Central  Google Scholar 

  30. Zininga T et al (2018) Heat shock proteins as immunomodulants. Molecules (Basel, Switzerland) 23

  31. He S et al (2019) Dietary resveratrol supplementation inhibits heat stress-induced high-activated innate immunity and inflammatory response in spleen of yellow-feather broilers. Poult Sci 98:6378–6387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chauhan SS et al (2014) Dietary antioxidants at supranutritional doses modulate skeletal muscle heat shock protein and inflammatory gene expression in sheep exposed to heat stress. J Anim Sci 92:4897–4908

    Article  CAS  PubMed  Google Scholar 

  33. Shehata AM et al (2020) Modulation of heat-shock proteins mediates chicken cell survival against thermal stress. Animals

  34. Duntas LH (2012) The evolving role of selenium in the treatment of graves’ disease and ophthalmopathy. J Thyroid Res 2012:736161

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Ishfaq M et al (2019) Baicalin ameliorates oxidative stress and apoptosis by restoring mitochondrial dynamics in the spleen of chickens via the opposite modulation of NF-κB and Nrf2/HO-1 signaling pathway during Mycoplasma gallisepticum infection. Poult Sci 98:6296–6310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Tan S et al (2017) Alleviation mechanisms of selenium on cadmium-spiked neutrophil injury to chicken. Biol Trace Elem Res 178:301–309

    Article  CAS  PubMed  Google Scholar 

  37. Yang X et al (2020) The activation of heat-shock protein after copper(II) and/or arsenic(III)-induced imbalance of homeostasis, inflammatory response in chicken rectum. Biol Trace Elem Res 195:613–623

    Article  CAS  PubMed  Google Scholar 

  38. Fan RF et al (2020) Selenium relieves oxidative stress, inflammation, and apoptosis within spleen of chicken exposed to mercuric chloride. Poult Sci 99:5430–5439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Fan R et al (2017) Gene silencing of selenoprotein K induces inflammatory response and activates heat shock proteins expression in chicken myoblasts. Biol Trace Elem Res 180:135–145

    Article  CAS  PubMed  Google Scholar 

  40. Du Q et al (2016) Selenium deficiency influences the expression of selenoproteins and inflammatory cytokines in chicken aorta vessels. Biol Trace Elem Res 173:501–513

    Article  CAS  PubMed  Google Scholar 

  41. Zhang Y et al (2020) Selenium deficiency induces inflammation via the iNOS/NF-κB pathway in the brain of pigs. Biol Trace Elem Res 196:103–109

    Article  CAS  PubMed  Google Scholar 

  42. Bai Y et al (2021) Selenium deficiency causes inflammatory injury in the bursa of fabricius of broiler chickens by activating the toll-like receptor signaling pathway. Biol Trace Elem Res 1–10

  43. Zhang Y et al (2021) Selenium deficiency induced necroptosis, Th1/Th2 imbalance, and inflammatory responses in swine ileum. J Cell Physiol 236:222–234

    Article  CAS  PubMed  Google Scholar 

  44. Yang HH et al (2012) Attenuating heat-induced acute lung inflammation and injury by dextromethorphan in rats. Am J Respir Cell Mol Biol 46:407–413

    Article  CAS  PubMed  Google Scholar 

  45. Baeuerle PA, Henkel T (1994) Function and activation of NF-kappa B in the immune system. Annu Rev Immunol 12:141–179

    Article  CAS  PubMed  Google Scholar 

  46. Zhao H et al (2021) ROS-Induced Hepatotoxicity under cypermethrin: involvement of the crosstalk between Nrf2/Keap1 and NF-κB/iκB-α pathways regulated by proteasome. Environ Sci Technol 55:6171–6183

    Article  CAS  PubMed  Google Scholar 

  47. Zheng L et al (2017) Jianpi Qingchang decoction alleviates ulcerative colitis by inhibiting nuclear factor-κB activation. World J Gastroenterol 23:1180–1188

    Article  PubMed  PubMed Central  Google Scholar 

  48. Wang W et al (2018) H(2)S induces Th1/Th2 imbalance with triggered NF-κB pathway to exacerbate LPS-induce chicken pneumonia response. Chemosphere 208:241–246

    Article  CAS  PubMed  Google Scholar 

  49. Batra S et al (2011) Nuclear factor-κB: a key regulator in health and disease of lungs. Arch Immunol Ther Exp 59:335–351

    Article  CAS  Google Scholar 

  50. Li S et al (2021) Selenium deficiency induces spleen pathological changes in pigs by decreasing selenoprotein expression, evoking oxidative stress, and activating inflammation and apoptosis. J Anim Sci Biotechnol 12:65

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Zhang HJ et al (2003) Heat-induced liver injury in old rats is associated with exaggerated oxidative stress and altered transcription factor activation. FASEB J 17:2293–2295

    Article  CAS  PubMed  Google Scholar 

  52. Liu Z et al (2020) Expression profiles of genes associated with inflammatory responses and oxidative stress in lung after heat stroke. Biosci Reports 40

  53. Wu T, Tanguay RM (2006) Antibodies against heat shock proteins in environmental stresses and diseases: friend or foe? Cell Stress Chaperones 11:1–12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Kol A et al (2000) Cutting edge: heat shock protein (HSP) 60 activates the innate immune response: CD14 is an essential receptor for HSP60 activation of mononuclear cells. J Immunol (Baltimore, Md. :1950) 164:13–17

    Article  CAS  Google Scholar 

  55. Martine P, Rébé C (2019) Heat shock proteins and inflammasomes. Int J Mol Sci 20

  56. Qiu XB et al (2006) The diversity of the DnaJ/Hsp40 family, the crucial partners for Hsp70 chaperones. Cell Mol Life Sci 63:2560–2570

    Article  CAS  PubMed  Google Scholar 

  57. Bascos NAD et al (2017) The Hsp40 J-domain modulates Hsp70 conformation and ATPase activity with a semi-elliptical spring. Protein Sci 26:1838–1851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Asea A et al (2000) HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 6:435–442

    Article  CAS  PubMed  Google Scholar 

  59. Li N et al (2021) Major signaling pathways and key mediators of macrophages in acute kidney injury (Review). Mol Med Rep 23

  60. Lu H et al (2019) Sedum sarmentosum Bunge extract alleviates inflammation and kidney injury via inhibition of M1-macrophage polarization. Phytomedicine 62:152976

    Article  CAS  PubMed  Google Scholar 

  61. Porta C et al (2015) Molecular and epigenetic basis of macrophage polarized activation. Semin Immunol 27:237–248

    Article  CAS  PubMed  Google Scholar 

  62. Zhou X et al (2019) YAP aggravates inflammatory bowel disease by regulating M1/M2 macrophage polarization and gut microbial homeostasis. Cell Reports 27:1176-1189 e1175

    Article  CAS  PubMed  Google Scholar 

  63. Zhang J et al (2016) IL-35 decelerates the inflammatory process by regulating inflammatory cytokine secretion and M1/M2 macrophage ratio in psoriasis. J Immunol (Baltimore, Md.: 1950) 197:2131–2144

    Article  CAS  Google Scholar 

  64. Chu F et al (2018) The roles of macrophages and microglia in multiple sclerosis and experimental autoimmune encephalomyelitis. J Neuroimmunol 318:1–7

    Article  CAS  PubMed  Google Scholar 

  65. Shapouri-Moghaddam A et al (2018) Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol 233:6425–6440

    Article  CAS  PubMed  Google Scholar 

  66. Lu H et al (2018) Quercetin ameliorates kidney injury and fibrosis by modulating M1/M2 macrophage polarization. Biochem Pharmacol 154:203–212

    Article  PubMed  CAS  Google Scholar 

  67. Bastos KR et al (2002) Macrophages from IL-12p40-deficient mice have a bias toward the M2 activation profile. J Leukoc Biol 71:271–278

    Article  CAS  PubMed  Google Scholar 

  68. Zhao Y et al (2020) Inhibition of the endoplasmic reticulum (ER) stress-associated IRE-1/XBP-1 pathway alleviates acute lung injury via modulation of macrophage activation. J Thorac Dis 12:284–295

    Article  PubMed  PubMed Central  Google Scholar 

  69. Fukui S et al (2017) M1 and M2 monocytes in rheumatoid arthritis: a contribution of imbalance of M1/M2 monocytes to osteoclastogenesis. Front Immunol 8:1958

    Article  PubMed  CAS  Google Scholar 

  70. Jang SE et al (2013) Lactobacillus brevis G-101 ameliorates colitis in mice by inhibiting NF-κB, MAPK and AKT pathways and by polarizing M1 macrophages to M2-like macrophages. J Appl Microbiol 115:888–896

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank the Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment and College of Veterinary Medicine, Northeast Agricultural University. We also thank the Students Innovation Training Program (SIPT) project of Northeast Agricultural University for support.

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Yilin Yin: Investigation, Formal analysis, Writing-original draft. Jinming Guo: Visualization. Zhaoyi Liu: Software, Resources. Shiwen Xu: Validation, Funding acquisition. Shufang Zheng: Conceptualization, Methodology, Supervision, Writing-review and editing. All authors have read the manuscript and agreed to submit it in its current form for consideration for publication in the Journal.

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Correspondence to Shufang Zheng.

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All procedures used in this study were approved by the Institutional Animal Care and Use Committee of Northeast Agricultural University (SRM-11).

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Yin, Y., Guo, J., Liu, Z. et al. Selenium Deficiency Aggravates Heat Stress Pneumonia in Chickens by Disrupting the M1/M2 Balance. Biol Trace Elem Res 200, 3315–3325 (2022). https://doi.org/10.1007/s12011-021-02905-w

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