Skip to main content
SpringerLink
Log in

Macrophage Polarization Induced by Probiotic Bacteria: a Concise Review

  • Published:
Probiotics and Antimicrobial Proteins Aims and scope Submit manuscript

Abstract

Macrophages display remarkable plasticity and can possess distinct functions in response to different environmental stimuli. Classically activated macrophages (M1 macrophages) are pro-inflammatory and have a critical role in host defense against infection, while alternatively activated macrophages (M2 macrophages) suppress inflammatory responses and associated with wound repair. Probiotic bacteria are reported to have a beneficial effect on the host immune status through their ability to modulate the macrophage polarization. Some probiotic strains are reported to activate macrophages to M1 phenotype to kill intracellular pathogens, while some other probiotics can induce M2 macrophages to exert the anti-inflammatory effect. Thus, this review will focus on the immunomodulatory role of probiotics in macrophage polarization and summarize the mode of action of probiotics in regulating macrophage plasticity. The detailed understanding of the immunomodulatory signaling effects of probiotic bacteria will broaden our understanding of how probiotics may regulate the immune system and find their therapeutic potentials for inflammatory diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Gordon S, Taylor PR (2005) Monocyte and macrophage heterogeneity. Nat Rev Immunol 5:953–964. https://doi.org/10.1038/nri1733

    Article  PubMed  CAS  Google Scholar 

  2. Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3:23–35. https://doi.org/10.1038/nri978

    Article  PubMed  CAS  Google Scholar 

  3. Martinez FO, Sica A, Mantovani A, Locati M (2008) Macrophage activation and polarization. Front Biosci 13:453–461. https://doi.org/10.2741/2692

    Article  PubMed  CAS  Google Scholar 

  4. Ji J, Hu S, Cui Z, Li W (2013) Probiotic Bacillus amyloliquefaciens mediate M1 macrophage polarization in mouse bone marrow-derived macrophages. Arch Microbiol 195:349–356. https://doi.org/10.1007/s00203-013-0877-7

    Article  PubMed  CAS  Google Scholar 

  5. Hill C, Guarner F, Reid G et al (2014) Expert consensus document: the international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 11:506–514. https://doi.org/10.1038/nrgastro.2014.66

    Article  PubMed  Google Scholar 

  6. Wu RY, Jeffery MP, Johnson-Henry KC, Green-Johnson JM, Sherman PM (2017) Impact of prebiotics, probiotics, and gut derived metabolites on host immunity. LymphoSign J 4:1–24. https://doi.org/10.14785/lymphosign-2016-0012

    Article  Google Scholar 

  7. Amy L, Andrew F (2017) Probiotic modulation of innate cell pathogen sensing and signaling events. Nutrients 9:1156. https://doi.org/10.3390/nu9101156

    Article  CAS  Google Scholar 

  8. Peters VBM, van de Steeg E, van Bilsen J, Meijerink M (2019) Mechanisms and immunomodulatory properties of pre- and probiotics. Benefic Microbes 10:225–236. https://doi.org/10.3920/BM2018.0066

    Article  CAS  Google Scholar 

  9. La Fata G, Weber P, Hasan Mohajeri H (2017) Probiotics and the gut immune system: indirect regulation. Probiotics Antimicro Prot 10:11–21. https://doi.org/10.1007/s12602-017-9322-6

    Article  CAS  Google Scholar 

  10. Jang SE, Hyam SR, Han MJ, Kin SY, Lee BG, Kim DH (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. https://doi.org/10.1111/jam.12273

    Article  PubMed  CAS  Google Scholar 

  11. Isidro RA, Bonilla FJ, Pagan H et al (2014) The probiotic mixture VSL#3 alters the morphology and secretion profile of both polarized and unpolarized human macrophages in a polarization-dependent manner. J Clin Cell Immunol 5:227. https://doi.org/10.4172/2155-9899.1000227

    Article  CAS  Google Scholar 

  12. Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8:958–969. https://doi.org/10.1038/nri2448

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Murray PJ (2017) Macrophage polarization. Annu Rev Physiol 79:541. https://doi.org/10.1146/annurev-physiol-022516-034339

    Article  PubMed  CAS  Google Scholar 

  14. Cassetta L, Cassol E, Poli G (2011) Macrophage polarization in health and disease. Sci World J 11:2391–2402. https://doi.org/10.1100/2011/213962

    Article  CAS  Google Scholar 

  15. Gordon S, Martinez FO (2010) Alternative activation of macrophages: mechanism and functions. Immunity 32:593–604. https://doi.org/10.1016/j.immuni.2010.05.007

    Article  PubMed  CAS  Google Scholar 

  16. Labonte AC, Tosello-Trampont AC, Hahn YS (2014) The role of macrophage polarization in infectious and inflammatory diseases. Mol Cell 37:275–285. https://doi.org/10.14348/molcells.2014.2374

    Article  CAS  Google Scholar 

  17. Laskin DL (2009) Macrophages and inflammatory mediators in chemical toxicity: a battle of forces. Chem Res Toxicol 22:1376–1385. https://doi.org/10.1021/tx900086v

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Wynn TA, Chawla A, Pollard JW (2013) Macrophage biology in development, homeostasis and disease. Nature 496:445–455. https://doi.org/10.1038/nature12034

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Shaughnessy LM, Swanson JA (2007) The role of the activated macrophage in clearing Listeria monocytogenes infection. Front Biosci 12:2683–2692. https://doi.org/10.2741/2364

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Benoit M, Desnues B, Mege JL (2008) Macrophage polarization in bacterial infections. J Immunol 181:3733–3739. https://doi.org/10.4049/jimmunol.181.6.3733

    Article  PubMed  CAS  Google Scholar 

  21. Pfeffer K, Matsuyama T, Kundig TM, Wakeham A, Kishihara K, Shahinian A, Wiegmann K, Ohashi PS, Kronke M, Mak TW (1993) Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell 73:457–467. https://doi.org/10.1016/0092-8674(93)90134-C

    Article  PubMed  CAS  Google Scholar 

  22. Stearns-Kurosawa DJ, Osuchowski MF, Valentine C, Kurosawa S, Remick DG (2011) The pathogenesis of sepsis. Annu Rev Pathol-Mech 6:19–48. https://doi.org/10.1146/annurev-pathol-011110-130327

    Article  CAS  Google Scholar 

  23. Mehta A, Brewington R, Chatterji M, Zoubine M, Kinasewitz GT, Peer GT, Cgang AC, Taylor FB Jr, Shnyra A (2004) Infection-induced modulation of M1 and M2 phenotypes in circulating monocytes: role in immune monitoring and early prognosis of sepsis. Shock 22:423–430. https://doi.org/10.1097/01.shk.0000142184.49976.0c

    Article  PubMed  CAS  Google Scholar 

  24. Bozza FA, Salluh JI, Japiassu AM, Soares M, Assis EF, Gomes RN, Bozza MT, Castro-Faria-Neto HC, Bozza PT (2007) Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis. Crit Care 11:R49. https://doi.org/10.1186/cc5783

    Article  PubMed  PubMed Central  Google Scholar 

  25. Murray PJ, Wynn TA (2011) Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 11:723–737. https://doi.org/10.1038/nri3073

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Liu Y, Zou X, Chai Y, Yao Y (2014) Macrophage polarization in inflammatory diseases. Int J Biol Sci 10:520–529. https://doi.org/10.7150/ijbs.8879

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Moos V, Schmidt C, Geelhaar A et al (2010) Impaired immune functions of monocytes and macrophages in whipple’s disease. Gastroenterology 138:210–220. https://doi.org/10.1053/j.gastro.2009.07.066

    Article  PubMed  CAS  Google Scholar 

  28. Thurlow LR, Hanke ML, Fritz T, Angle A, Aldrich A, Williams SH, Engebretsen LE, Bayles KW, Horswill AR, Kielian T (2011) Staphylococcus aureus biofilms prevent macrophage phagocytosis and attenuate inflammation in vivo. J Immunol 186:6585–6596. https://doi.org/10.4049/jimmunol.1002794

    Article  PubMed  CAS  Google Scholar 

  29. Shirey KA, Cole LE, Keegan AD, Vogel SN (2008) Francisella tularensis live vaccine strain induces macrophage alternative activation as a survival mechanism. J Immunol 181:4159. https://doi.org/10.1016/j.jpedsurg.2009.01.041

    Article  PubMed  CAS  Google Scholar 

  30. Zhao Y, Yang J, Gao YD, Guo W (2010) Th17 immunity in patients with allergic asthma. Int Arch Allergy Immunol 151:297–307. https://doi.org/10.1159/000250438

    Article  PubMed  CAS  Google Scholar 

  31. Saradna A, Do DC, Kumar S, Fu QL, Gao P (2017) Macrophage polarization and allergic asthma. Transl Res 191. https://doi.org/10.1016/j.trsl.2017.09.002

  32. Girodet P-OO, Nguyen D, Mancini JD, Hundal M, Zhou X, Israel E, Cernadas M (2016) Alternative macrophage activation is increased in asthma. Am J Resp Cell Mol 55:467–475. https://doi.org/10.1165/rcmb.2015-0295OC

    Article  CAS  Google Scholar 

  33. Robbe P, Draijer C, Borg TR, Luinge M, Timens W, Wouters IM, Melgert BN, Hylkema MN (2015) Distinct macrophage phenotypes in allergic and nonallergic lung inflammation. Am J Physiol-Lung C 308:L358–L367. https://doi.org/10.1152/ajplung.00341.2014

    Article  CAS  Google Scholar 

  34. Nabe T, Wakamori H, Yano C, Nishiguchi A, Yuasa R, Kido H, Tomiyama Y, Tomoda A, Kida H, Takiguchi A, Matsuda M, Ishihara K, Akiba S, Ohya S, Fukui H, Mizutani N, Yoshino S (2015) Production of interleukin (IL)-33 in the lungs during multiple antigen challenge-induced airway inflammation in mice, and its modulation by a glucocorticoid. Eur J Pharmacol 757:34–41. https://doi.org/10.1016/j.ejphar.2015.03.015

    Article  PubMed  CAS  Google Scholar 

  35. Joshi AD, Oak SR, Hartigan AJ, Finn WG, Kunkel SL, Duffy KE, Das A, Hogaboam CM (2010) Interleukin-33 contributes to both M1 and M2 chemokine marker expression in human macrophages. BMC Immunol 11:52. https://doi.org/10.1186/1471-2172-11-52

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Kurowska-Stolarska M, Stolarski B, Kewin P et al (2009) IL-33 amplifies the polarization of alternatively activated macrophages that contribute to airway inflammation. J Immunol 183:6469–6477. https://doi.org/10.4049/jimmunol.0901575

    Article  PubMed  CAS  Google Scholar 

  37. Lumeng CN, Bodzin JL, Saltiel AR (2007) Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117:175–184. https://doi.org/10.1172/JCI29881

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Lumeng CN, DelProposto JB, Westcott DJ, Saltiel AR (2008) Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes 57:3239–3246. https://doi.org/10.2337/db08-0872

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Zhou D, Huang C, Lin Z, Zhan S, Kong L, Fang C, Li J (2013) Macrophage polarization and function with emphasis on the evolving roles of coordinated regulation of cellular signaling pathways. Cell Signal 26:192–197. https://doi.org/10.1016/j.cellsig.2013.11.004

    Article  PubMed  CAS  Google Scholar 

  40. Gisterå A, Hansson GK (2017) The immunology of atherosclerosis. Nat Rev Nephrol 13:368–380. https://doi.org/10.1038/nrneph.2017.51

    Article  PubMed  CAS  Google Scholar 

  41. Khallou-Laschet J, Varthaman A, Fornasa G, Compain C, Gaston AT, Clement M, Dussiot M, Levillain O, Graff-Dubois S, Nicoletti A, Caligiuri G (2010) Macrophage plasticity in experimental atherosclerosis. PLoS One 5:e8852. https://doi.org/10.1371/journal.pone.0008852

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Rooks MG, Garrett WS (2016) Gut microbiota, metabolites and host immunity. Nat Rev Immunol 16:341–352. https://doi.org/10.1038/nri.2016.42

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Kim YG, Udayanga KGS, Totsuka N, Weinberg JB, Nunez G, Shibuya A (2014) Gut dysbiosis promotes M2 macrophage polarization and allergic airway inflammation via fungi-induced PGE2. Cell Host Microbe 15:95–102. https://doi.org/10.1016/j.chom.2013.12.010

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Ji J, Shu D, Zheng M, Wang J, Luo C, Wang Y, Guo F, Zou X, Lv X, Li Y, Liu T, Qu H (2016) Microbial metabolite butyrate facilitates M2 macrophage polarization and function. Sci Rep-UK 6:24838. https://doi.org/10.1038/srep24838

    Article  CAS  Google Scholar 

  45. Yang Y, Wang X, Huycke T, Moore DR, Lightfoot SA, Hucke MM (2013) Colon macrophages polarized by commensal bacteria cause colitis and cancer through the bystander effect. Transl Oncol 6:596–606. https://doi.org/10.1593/tlo.13412

    Article  PubMed  PubMed Central  Google Scholar 

  46. Compare D, Coccoli P, Rocco A, Nardone OM, De Maria S, Carteni M, Nardone G (2012) Gut-liver axis: the impact of gut microbiota on non alcoholic fatty liver disease. Nutr Metab Cardiovasc 22:471–476. https://doi.org/10.1016/j.numecd.2012.02.007

    Article  CAS  Google Scholar 

  47. Isidro RA, Lopez A, Cruz ML, Gonzalez Torres MI, Chompre G, Isidro AA, Appleyard CB (2017) The probiotic VSL#3 modulates colonic macrophages, inflammation, and microflora in acute trinitrobenzene sulfonic acid colitis. J Histochem Cytochem 65:22155417718542. https://doi.org/10.1369/0022155417718542

    Article  CAS  Google Scholar 

  48. Sun L, Liu H, Jiang H, Wei M, Liang S, Wang M, Shi K, He Q (2016) Macrophages are involved in gut bacterial translocation and reversed by Lactobacillus in experimental uremia. Dig Dis Sci 61:1534–1544. https://doi.org/10.1007/s10620-015-3950-z

    Article  PubMed  CAS  Google Scholar 

  49. Wang Y, Du W, Lei K, Wang B, Wang Y, Zhou Y, Li W (2017) Effects of dietary Bacillus licheniformis on gut physical barrier, immunity, and reproductive hormones of laying hens. Probiotics Antimicro Prot 9:292–299. https://doi.org/10.1007/s12602-017-9252-3

    Article  CAS  Google Scholar 

  50. Wang Y, Gong L, Wu Y, Cui Z, Wang Y, Huang Y, Zhang X, Li W (2019) Oral administration of Lactobacillus rhamnosus GG to newborn piglets augments gut barrier function in pre-weaning piglets. J Zhejiang Univ Sci B 20:180–192. https://doi.org/10.1631/jzus.B1800022

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Wang Y, Wu Y, Wang B, Xu H, Mei X, Xu X, Zhang X, Ni J, Li W (2019) Bacillus amyloliquefaciens SC06 protects mice against high-fat diet-induced obesity and liver injury via regulating host metabolism and gut microbiota. Front Microbiol 10:1161. https://doi.org/10.3389/fmicb.2019.01161

    Article  PubMed  PubMed Central  Google Scholar 

  52. Christoffersen TE, Hult LTO, Kuczkowska K, Moe KM, Skele S, Lea T, Kleiveland CR (2014) In vitro comparison of the effects of probiotic, commensal and pathogenic strains on macrophage polarization. Probiotics Antimicro Prot 6:1–10. https://doi.org/10.1007/s12602-013-9152-0

    Article  CAS  Google Scholar 

  53. Guha D, Banerjee A, Mukherjee R (2019) A probiotic formulation containing Lactobacillus bulgaricus DWT1 inhibits tumor growth by activating pro-inflammatory responses in macrophages. J Funct Foods 56:232–245. https://doi.org/10.1016/j.jff.2019.03.030

    Article  CAS  Google Scholar 

  54. Guo L, Meng M, Wei Y, Lin F, Jiang Y, Cui X, Wang G, Wang C, Guo X (2019) Protective effects of live combined B. subtilis and E. faecium in polymicrobial sepsis through modulating activation and transformation of macrophages and mast cells. Front Pharmacol 9:1506. https://doi.org/10.3389/fphar.2018.01506

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Neuman MG, Nanau RM (2012) Inflammatory bowel disease: role of diet, microbiota, life style. Transl Res 160:29–44. https://doi.org/10.1016/j.trsl.2011.09.001

    Article  PubMed  Google Scholar 

  56. Rafii F, Ruseler-Van Embden JG, van Lieshout LM (1999) Changes in bacterial enzymes and PCR profiles of fecal bacteria from a patient with ulcerative colitis before and after antimicrobial treatments. Dig Dis Sci 44:637–642. https://doi.org/10.1023/A:1026634229934

    Article  PubMed  CAS  Google Scholar 

  57. Shanahan F (2002) Gut flora in gastrointestinal disease. Eur J Surg Suppl 587:47–52. https://doi.org/10.1080/110241502317307562

    Article  Google Scholar 

  58. Fedorak RN, Gionchetti P, Campieri M, Madsen K, Isaacs K, Desimone C, Sartor B (2013) VSL3 probiotic mixture induces remission in patients with active ulcerative colitis. Gastroenterology 124:A377. https://doi.org/10.1016/S0016-5085(03)81909-1

    Article  Google Scholar 

  59. Daniel C, Poiret S, Goudercourt D, Dennin V, Leyer G, Pot B (2006) Selecting lactic acid bacteria for their safety and functionality by use of a mouse colitis model. Appl Environ Microbiol 72:5799–5805. https://doi.org/10.1128/AEM.00109-06

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Peran L, Sierra S, Comalada M et al (2007) A comparative study of the preventative effects exerted by two probiotics, Lactobacillus reuteri and Lactobacillus fermentum, in the trinitrobenzenesulfonic acid model of rat colitis. Br J Nutr 97:96–103. https://doi.org/10.1017/s0007114507257770

    Article  PubMed  CAS  Google Scholar 

  61. Jang SE, Han MJ, Kim SY, Kim DH (2014) Lactobacillus plantarum CLP-0611 ameliorates colitis in mice by polarizing M1 to M2-like macrophages. Int Immunopharmacol 21:186–192. https://doi.org/10.1016/j.intimp.2014.04.021

    Article  PubMed  CAS  Google Scholar 

  62. Lim SM, Jeong JJ, Jang SE, Han MJ, Kim DH (2016) A mixture of the probiotic strains Bifidobacterium longum CH57 and Lactobacillus brevis CH23 ameliorates colitis in mice by inhibiting macrophage activation and restoring the Th17/Treg balance. J Funct Foods 27:295–309. https://doi.org/10.1016/j.jff.2016.09.011

    Article  CAS  Google Scholar 

  63. Sohn W, Jun DW, Lee KN, Lee HL, Lee OY, Choi HS, Yoon BC (2015) Lactobacillus paracasei induces M2-dominant kupffer cell polarization in a mouse model of nonalcoholic steatohepatitis. Dig Dis Sci 60:3340–3350. https://doi.org/10.1007/s10620-015-3770-1

    Article  PubMed  CAS  Google Scholar 

  64. Woo JY, Gu W, Kim KA, Jang SE, Han MJ, Kim DH (2014) Lactobacillus pentosus var. plantarum C29 ameliorates memory impairment and inflammaging in a D-galactose-induced accelerated aging mouse model. Anaerobe 27:22–26. https://doi.org/10.1016/j.anaerobe.2014.03.003

    Article  PubMed  CAS  Google Scholar 

  65. Paynich ML, Jones-Burrage SE, Knight KL (2017) Exopolysaccharide from Bacillus subtilis induces anti-inflammatory M2 macrophages that prevent T cell–mediated disease. J Immunol 198:2689–2698. https://doi.org/10.4049/jimmunol.1601641

    Article  PubMed  CAS  Google Scholar 

  66. Paik W, Alonzo F, Knight KL (2019) Probiotic exopolysaccharide protects against systemic Staphylococcus aureus infection, inducing dual-functioning macrophages that restrict bacterial growth and limit inflammation. Infect Immun. https://doi.org/10.1128/iai.00791-18

  67. Kim DH, Kim S, Lee JH et al (2019) Lactobacillus acidophilus suppresses intestinal inflammation by inhibiting endoplasmic reticulum stress. J Gastroenterol Hepatol 34:178–185. https://doi.org/10.1111/jgh.14362

    Article  PubMed  CAS  Google Scholar 

  68. Kim SO, Sheikh HI, Ha SD, Matins A, Reid G (2007) G-CSF-mediated inhibition of JNK is a key mechanism for Lactobacillus rhamnosus-induced suppression of TNF production in macrophages. Cell Microbiol 8:1958–1971. https://doi.org/10.1111/j.1462-5822.2006.00763.x

    Article  CAS  Google Scholar 

  69. Lin YP, Thibodeaux CH, Peña JA, Ferry GD, Versalovic J (2008) Probiotic Lactobacillus reuteri suppress proinflammatory cytokines via c-Jun. Inflamm Bowel Dis 14:1068–1083. https://doi.org/10.1002/ibd.20448

    Article  PubMed  Google Scholar 

  70. Latvala S, Miettinen M, Kekkonen RA, Korpela R, Julkunen I (2011) Lactobacillus rhamnosus GG and Streptococcus thermophilus induce suppressor of cytokine signalling 3 (SOCS3) gene expression directly and indirectly via interleukin-10 in human primary macrophages. Clin Exp Immunol 165:94–103. https://doi.org/10.1111/j.1365-2249.2011.04408.x

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Lawrence T, Natoli G (2011) Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat Rev Immunol 11:750–761. https://doi.org/10.1038/nri3088

    Article  PubMed  CAS  Google Scholar 

  72. Hyam SR, Lee IA, Gu W, Kin KA, Jeong JJ, Jang SE, Han MJ, Kim DH (2013) Arctigenin ameliorates inflammation in vitro and in vivo by inhibiting the PI3K/AKT pathway and polarizing M1 macrophages to M2-like macrophages. Eur J Pharmacol 708:21–29. https://doi.org/10.1016/j.ejphar.2013.01.014

    Article  PubMed  CAS  Google Scholar 

  73. Rocher C, Singla DK (2013) SMAD-PI3K-Akt-mTOR pathway mediates BMP-7 polarization of monocytes into M2 macrophages. PLoS One 8. https://doi.org/10.1371/journal.pone.0084009

  74. Mao Y, Wang B, Xu X, Du W, Li W, Wang Y (2015) Glycyrrhizic acid promotes M1 macrophage polarization in murine bone marrow-derived macrophages associated with the activation of JNK and NF-κB. Mediat Inflamm 2015:372931. https://doi.org/10.1155/2015/372931

    Article  CAS  Google Scholar 

  75. Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V, Mukundan L, Red Eagle A, Vats D, Brombacher F, Ferrante AW, Chawla A (2007) Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature 447:1116–1120. https://doi.org/10.1038/nature05894

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Bouhlel MA, Derudas B, Rigamonti E et al (2007) PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab 6:137–143. https://doi.org/10.1016/j.cmet.2007.06.010

    Article  PubMed  CAS  Google Scholar 

  77. Iwaki M, Matsuda M, Maeda N, Funahashi T, Matsuzawa Y, Makishima M, Shimomura I (2003) Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors. Diabetes 52:1655–1663. https://doi.org/10.2337/diabetes.52.7.1655

    Article  PubMed  CAS  Google Scholar 

  78. Chow JC, Young DW, Golenbock DT, Christ WJ, Gusovsky F (1999) Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. J Biol Chem 274:10689–10692. https://doi.org/10.1074/jbc.274.16.10689

    Article  PubMed  CAS  Google Scholar 

  79. Cario E, Podolsky DK (2000) Differential alteration in intestinal epithelial cell expression of Toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun 68:7010–7017. https://doi.org/10.1128/IAI.68.12.7010-7017.2000

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Liu CP, Zhang X, Tan QL, Xu WX, Zhou CY, Luo M, Li X, Zeng X (2017) NF-kappaB pathways are involved in M1 polarization of RAW 264.7 macrophage by polyporus polysaccharide in the tumor microenvironment. PLoS One 12:e0188317. https://doi.org/10.1371/journal.pone.0188317

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Camille N, Dealtry G (2018) Regulation of M1/M2 macrophage polarization by, Sutherlandia frutescens via, NFkB and MAPK signaling pathways. S Afr J Bot 116:42–51. https://doi.org/10.1016/j.sajb.2018.02.400

    Article  CAS  Google Scholar 

  82. Guha M, Mackman N (2002) The phosphatidylinositol 3-kinase-Akt pathway limits lipopolysaccharide activation of signaling pathways and expression of inflammatory mediators in human monocytic cells. J Biol Chem 277:32124–32132. https://doi.org/10.1074/jbc.m203298200

    Article  PubMed  CAS  Google Scholar 

  83. Fukao T, Koyasu S (2003) PI3K and negative regulation of TLR signaling. Trends Immunol 24:358–363. https://doi.org/10.1016/s1471-4906(03)00139-x

    Article  PubMed  CAS  Google Scholar 

  84. Hunter T (1995) When is a lipid kinase not a lipid kinase? When it is a protein kinase. Cell 83:1–4. https://doi.org/10.1016/0092-8674(95)90225-2

    Article  PubMed  CAS  Google Scholar 

  85. Katso R, Okkenhaug K, Ahmadi K, White S, Timms J, Waterfield MD (2001) Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer. Annu Rev Cell Dev Biol 17:615–675. https://doi.org/10.1146/annurev.cellbio.17.1.615

    Article  PubMed  CAS  Google Scholar 

  86. Saponaro C, Cianciulli A, Calvello R, Dragone T, Lacobazzi F, Panaro MA (2012) The PI3K/Akt pathway is required for LPS activation of microglial cells. Immunopharmacol Immunotoxicol 34:858–865. https://doi.org/10.3109/08923973.2012.665461

    Article  PubMed  CAS  Google Scholar 

  87. Wang J, Xie L, Wang S, Lin J, Liang J, Xu J (2018) Azithromycin promotes alternatively activated macrophage phenotype in systematic lupus erythematosus via PI3K/Akt signaling pathway. Cell Death Dis 9:1080–1013. https://doi.org/10.1038/s41419-018-1097-5

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Arranz A, Doxaki C, Vergadi E et al (2012) Akt1 and Akt2 protein kinases differentially contribute to macrophage polarization. Proc Natl Acad Sci U S A 109:9517–9522. https://doi.org/10.1073/pnas.1119038109

    Article  PubMed  PubMed Central  Google Scholar 

  89. Seth A, Yan F, Polk DB, Rao RK (2008) Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC-and MAP kinase-dependent mechanism. Am J Physiol Gastrointest Liver Physiol 294:G1060–G1069. https://doi.org/10.1152/ajpgi.00202.2007

    Article  PubMed  CAS  Google Scholar 

  90. Quero L, Hanser E, Manigold T, Tiaden AN, Kyburz D (2017) TLR2 stimulation impairs anti-inflammatory activity of M2-like macrophages, generating a chimeric M1/M2 phenotype. Arthritis Res Ther 19:245–213. https://doi.org/10.1186/s13075-017-1447-1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Zhang B, Wei Y, Wang G, Li D, Shi J, Zhang F (2019) Targeting MAPK pathways by naringenin modulates microglia M1/M2 polarization in lipopolysaccharide-stimulated cultures. Front Cell Neurosci 12:531. https://doi.org/10.3389/fncel.2018.00531

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Ransone LJ, Verma IM (1990) Nuclear proto-oncogenes fos and jun. Annu Rev Cell Biol 6:539–557. https://doi.org/10.1146/annurev.cb.06.110190.002543

    Article  PubMed  CAS  Google Scholar 

  93. Shaulian E, Karin M (2002) AP-1 as a regulator of cell life and death. Nat Cell Biol 4:E131–E136. https://doi.org/10.1038/ncb0502-e131

    Article  PubMed  CAS  Google Scholar 

  94. Fujioka S, Niu J, Schmidt C, Sclabas GM, Peng B, Uwagawa T, Li Z, Evans DB, Abbruzzese JL, Chao PJ (2004) NF-kappaB and AP-1 connection: mechanism of NF-kappaB-dependent regulation of AP-1 activity. Mol Cell Biol 24:7806–7819. https://doi.org/10.1128/MCB.24.17.7806-7819.2004

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Hu X, Chen J, Wang L, Ivashkiv LB (2007) Crosstalk among JAK-STAT, toll-like receptor, and itam-dependent pathways in macrophage activation. J Leukoc Biol 82:237–243. https://doi.org/10.1189/jlb.1206763

    Article  PubMed  CAS  Google Scholar 

  96. Takeda K, Clausen BE, Kaisho T, Tsujimura T, Terada N, Forster I, Akira S (1999) Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity 10:39–49. https://doi.org/10.1016/S1074-7613(00)80005-9

    Article  PubMed  CAS  Google Scholar 

  97. Matsukawa A, Takeda K, Kudo S, Maeda T, Kagayama M, Akira S (2003) Aberrant inflammation and lethality to septic peritonitis in mice lacking STAT3 in macrophages and neutrophils. J Immunol 171:6198–6205. https://doi.org/10.4049/jimmunol.171.11.6198

    Article  PubMed  CAS  Google Scholar 

  98. Wang N, Liang H, Zen K (2014) Molecular mechanisms that influence the macrophage M1-M2 polarization balance. Front Immunol 5. https://doi.org/10.3389/fimmu.2014.00614

  99. Sica A, Bronte V (2007) Altered macrophage differentiation and immune dysfunction in tumor development. J Clin Invest 117:1155–1166. https://doi.org/10.1172/JCI31422

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Johnson-Henry KC, Nadjafi M, Avitzur Y, Mitchell DJ, Ngan BY, Galindo-Mata E, Jones NL, Sherman PM (2005) Amelioration of the effects of Citrobacter rodentium infection in mice by pretreatment with probiotics. J Infect Dis 191:2106–2117. https://doi.org/10.1086/430318

    Article  PubMed  Google Scholar 

  101. Harb H, van Tol EA, Heine H, Braaksma M, Gross G, Overkamp K, Hennen M, Alrifai M, Conrad ML, Renz H, Garn H (2013) Neonatal supplementation of processed supernatant from Lactobacillus rhamnosus GG improves allergic airway inflammation in mice later in life. Clin Exp Allergy 43:353–364. https://doi.org/10.1111/cea.12047

    Article  PubMed  CAS  Google Scholar 

  102. Kim JY, Kim H, Jung BJ, Kim NR, Park JE, Chung DK (2013) Lipoteichoic acid isolated from Lactobacillus plantarum suppresses LPS-mediated atherosclerotic plaque inflammation. Mol Cell 35:115–124. https://doi.org/10.1007/s10059-013-2190-3

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the Doctoral Science Research Startup Funding of Qingdao Agricultural University (663/1119042), the Natural Science Foundation of Shandong Province (ZR2017LC024), and the Qingdao Science and Technology Program (18-1-2-14-zhc).

Author information

Author notes

  1. Yang Wang and Huawei Liu contributed equally to this work.

Authors and Affiliations

  1. College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, 266109, China

    Yang Wang, Huawei Liu & Jinshan Zhao

Authors
  1. Yang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Huawei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jinshan Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed substantially to the conception and design of the manuscript. Yang Wang wrote the first draft of the manuscript. All authors contributed to revisions and approved the final version.

Corresponding authors

Correspondence to Yang Wang or Jinshan Zhao.

Ethics declarations

Conflict of Interest

The authors declare that there is no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Y., Liu, H. & Zhao, J. Macrophage Polarization Induced by Probiotic Bacteria: a Concise Review. Probiotics & Antimicro. Prot. 12, 798–808 (2020). https://doi.org/10.1007/s12602-019-09612-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12602-019-09612-y

Keywords

Search

Navigation