乳酸菌介导巨噬细胞极化作用的研究进展
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摘要
乳酸菌可以在肠道内定植,维持肠道菌群平衡,通过产生有机酸、细菌素等抗菌物质抑制肠道内有害菌的生长。大量研究表明乳酸菌发挥益生作用的主要机制可能与它的活化和维持机体免疫屏障机制及调节肠道生理屏障功能密切相关。乳酸菌作为益生菌与免疫细胞之间有着不可分割的关系,尤其是巨噬细胞。它通过各种途径与巨噬细胞作用,使巨噬细胞产生细胞因子,并向不同的表型极化,参与模式识别受体包括Toll样受体(TLRs)、Notch、核因子κB(NF-κB)信号通路等,从而降低机体的炎症反应。在这过程中,乳酸菌在机体调节中发挥重要作用。本文主要对乳酸菌介导巨噬细胞产生免疫调节的作用机制进行阐述。
Lactic acid bacteria was colonized in the intestine to maintain the balance of the intestinal microflora and inhibit the growth of harmful bacteria in the intestinal tract by producing antibacterial substances such as organic acids and bacteriocins. A large number of studies have shown that the main mechanism of Lactic acid bacteria may be closely related to matain immune balance and regulate physiological barrier of the intestinal tract. Lactobacillus,as the special strain,has superiority to activate and regulate the immune cells,especially macrophages. It interacts with macrophages through various pathways,causing macrophages to produce cytokines and polarize to different phenotypes,participating in pattern recognition receptors including Toll-like receptors( TLRs),Notch,and Nuclear factor kappa B( NF-кB) Signal pathways,etc. thereby reducing the body' s inflammatory response. This article describes the mechanism of Lactic acid bacteria-mediated macrophage immune regulation.
Lactic acid bacteria was colonized in the intestine to maintain the balance of the intestinal microflora and inhibit the growth of harmful bacteria in the intestinal tract by producing antibacterial substances such as organic acids and bacteriocins. A large number of studies have shown that the main mechanism of Lactic acid bacteria may be closely related to matain immune balance and regulate physiological barrier of the intestinal tract. Lactobacillus,as the special strain,has superiority to activate and regulate the immune cells,especially macrophages. It interacts with macrophages through various pathways,causing macrophages to produce cytokines and polarize to different phenotypes,participating in pattern recognition receptors including Toll-like receptors( TLRs),Notch,and Nuclear factor kappa B( NF-кB) Signal pathways,etc. thereby reducing the body' s inflammatory response. This article describes the mechanism of Lactic acid bacteria-mediated macrophage immune regulation.
引文
[1] Rajoka MSR,Shi J,Zhu J,et al. Capacity of lactic acid bacteria in immunity enhancement and cancer prevention[J]. Applied Microbiol Biotechnol,2017,101(1):35-45.
[2] Wang N,Liang H,Ke Z. Molecular mechanisms that influence the macrophage M1-M2 polarization balance[J]. Front Immunol,2014,5:614.
[3] Tassiulas I,Parkmin K H,Hu Y,et al. Apoptotic cells inhibit LPSinduced cytokine and chemokine production and IFN responses in macrophages[J]. Human Immunology,2007,68.
[4] Wang Y,Lin YX,Qiao SL,et al. Polymeric nanoparticles promote macrophage reversal from M2 to M1 phenotypes in the tumor microenvironment[J]. Biomaterials,2017,112:153-163.
[5] Wijesundera KK,Izawa T,Tennakoon AH,et al. M1-and M2-macrophage polarization in rat liver cirrhosis induced by thioacetamide(TAA),focusing on Iba1 and galectin-3[J]. Exp Mol Pathol,2014,96(3):382-396.
[6]郑新,王红艳. M2型巨噬细胞极化及相关疾病的研究进展[J].生命科学,2017,29(9):73-80.Zheng X,Wang HY. Research progress of M2 macrophage polarization and related diseases[J]. Life Sci,2017,29(9):73-80.
[7]靳丽媛,司艺玲,陈光辉.巨噬细胞表型极化在糖尿病心肌病发生发展和修复过程中的作用[J].解放军医学院学报,2017,38(1):68-70.Jin LY,Si YL,Chen GH. The role of macrophage phenotypic polarization in the development and repair of diabetic cardiomyopathy[J]. J PLA Univ Med Sci,2017,38(1):68-70.
[8] Wynn TA,Chawla A, Pollard JW. Macrophage biology in development,homeostasis and disease[J]. Nature,2013,496(7446):445-455.
[9] Luo F,Sun X,Qu Z,et al. Salmonella typhimurium-induced M1macrophage polarization is dependent on the bacterial O antigen[J]. World J Microbiol Biotechnol,2016,32(2):22-29.
[10] Chen S,Lu Z,Wang F,et al. Cathelicidin-WA polarizes E. coli K88-induced M1 macrophage to M2-like macrophage in RAW264. 7 cells[J]. Int Immunopharmacol,2017,54:52-64.
[11] Galdiero MR,Mantovani A. Macrophage plasticity and polarization[J]. J Clin Invest,2015,122(3):117-130.
[12] Yalcin AD,Bisgin A,Gorczynski RM. IL-8,IL-10,TGF-β,and GCSF levels were increased in severe persistent allergic asthma patients with the Anti-IgE treatment[J]. Mediat Inflamm,2012,2012(5):720-976.
[13] Page C,Goicochea L,Matthews K,et al. Induction of alternatively activated macrophages enhances pathogenesis during severe acute respiratory syndrome coronavirus infection.[J]. J Virol,2012,86(24):33-34.
[14] Reinartz S,Schumann T,Finkernagel F,et al. Mixed-polarization phenotype of ascites-associated macrophages in human ovarian carcinoma:Correlation of CD163 expression,cytokine levels and early relapse[J]. Int J Cancer,2014,134(1):32-42.
[15] Kong L,Zhang Q,Chao J,et al. Polarization of macrophages induced by Toxoplasma gondii and its impact on abnormal pregnancy in rats[J]. Acta Tropica,2015,143:1-7.
[16]刘勇,徐飞,管俊昌,等.金黄色葡萄球菌及其L型诱导小鼠腹腔巨噬细胞凋亡研究[J].中国人兽共患病学报,2005,21(8):735-735.Liu Y,Xu F,Guan JC,et al. Study on apoptosis of mouse peritoneal macrophages induced by Staphylococcus aureus and its L-type[J]. Chin J Zoonoses,2005,21(8):735-735.
[17]刘东方,薛梅,桑建,等.高黏附性乳酸菌的筛选及其对免疫细胞活性影响的研究[J].中国微生态学杂志,2016,28(8):869-874.Liu DF,Xue M,Sang J,et al. Screening of high adhesion lactic acid bacteria and its effect on immune cell activity[J]. Chin J Microecol,2016,28(8):869-874.
[18]刘红梅,李苏楠,吴婷婷,等. IL-21对LPS诱导的巨噬细胞中细胞因子IL-1β、IL-10、IL-12 mRNA表达的影响[J].中国兽医学报,2014,34(10):1653-1656.Liu HM,Li SN,Wu TT,et al. Effects of IL-21 on the expression of cytokines IL-1β,IL-10 and IL-12 mRNA in LPS-induced macrophages[J]. Chin J Vet Sci,2014,34(10):1653-1656.
[19]廖瑾莉,熊艳,刘志豪,等.慢性华支睾吸虫感染极化M2型巨噬细胞对脓毒症大鼠肺脏保护作用的研究[J].中华急诊医学杂志,2017,26(5):5-33.Liao XL,Xiong Y,Liu ZH,et al. Study on the protective effect of polarized M2 macrophages from chronic clonorchiasis on lung in septic rats[J]. Chin J Emerg Med,2017,26(5):5-33.
[20] Maghsood F,Mirshafiey A,Farahani MM,et al. Dual effects of cell free supernatants from lactobacillus acidophilus and lactobacillus rhamnosu SGG in regulation of MMP-9 by upregulating TIMP-1 and down-regulating CD147 in PMAdifferentiated THP-1 cells[J]. Cell J,2018,19(4):559-568.
[21] Wang J,Fang XB, Wu W. Immunomodulatory effects of Lactobacillus plantarum JLK0142 extracellular polysaccharide on RAW264. 7 macrophages and immunosuppressive mice[J]. Acta Microbiologica Sinica,2018:1-18.
[22] Ichikawa S,Fujii R,Fujiwara D,et al. My D88 but Not TLR2,4 or9 is essential for IL-12 induction by lactic acid bacteria[J].Biosci Biotechnol Biochem,2007,71(12):3026-3032.
[23] Christoffersen TE,Hult LT,Kuczkowska K,et al. In vitro comparison of the effects of probiotic,commensal and pathogenic strains on macrophage polarization[J]. Probiotics Antimicro,2014,6(1):1-10.
[24] Sohn W,Jun DW,Lee KN,et al. Lactobacillus paracasei induces M2-dominant kupffer cell polarization in a mouse model of nonalcoholic steatohepatitis[J]. Digest Dis Sci,2015,60(11):3340-3350.
[25] Ji J,Hu SL,Cui ZW,et al. Probiotic Bacillus amyloliquefaciens mediate M1 macrophage polarization in mouse bone marrowderived macrophages[J]. Arch Microbiol,2013,195(5):349-356.
[26] Saliba A E,Li L,Westermann A J,et al. Single-cell RNA-seq ties macrophage polarization to growth rate of intracellular Salmonella[J]. J Public Health Med,2016,19(4):380-397.
[27] Lo CS,Reverberi D,Balbi C,et al. Mesenchymal stem cellderived extracellular vesicles as mediators of anti-inflammatory effects:endorsement of macrophage polarization[J]. Stem Cells Translat Med,2017,6(3):1018-1028.
[28] Grote K,Schuett J,Schuett H,et al. Toll-like receptors in angiogenesis[J]. Sci World J,2017,11(1):981-991.
[29] Chen K,Xiang Y,Yao X,et al. The active contribution of Tolllike receptors to allergic airway inflammation[J]. Int Immunopharmacol,2011,11(10):1391-1398.
[30]张英春,马微,易华西,等.副干酪乳杆菌M5-L抑制宋内志贺氏菌黏附作用影响因素的研究[J].食品工业科技,2012,33(24):99-102.Zhang YC,Ma W,Yi HX,et al. Study on the factors influencing the adhesion of Lactobacillus paracasei M5-L to Shigella sinensis[J]. Food Sci Techol,2012,33(24):99-102.
[31] Shen CY,Zhang WL,Jiang JG. Immune-enhancing activity of polysaccharides from Hibiscus sabdariffa Linn. via MAPK and NF-κB signaling pathways in RAW264. 7 cells[J]. J Funct Foods,2017,34:118-129.
[32]石少华,王春凤. NF-κB信号传导通路在乳酸菌免疫调节中的作用[J].吉林农业大学学报,2012,34(5):566-570.Shi SH,Wang CF. The role of NF-κB signaling pathway in immune regulation of lactic acid bacteria[J]. J Jilin Agricultural Univ,2012,34(5):566-570.
[33]许光勇,苏敬良,姜金奇,等.乳酸调控大鼠肠黏膜微血管内皮细胞的NF-κB信号通路[J].中国实验动物学报,2012,20(4):80-86.Xu GY,Su JL,Jiang JQ,et al. Regulation of NF-κB signaling pathway in rat intestinal mucosal microvascular endothelial cells by lactic acid[J]. Chin J Exp Animal,2012,20(4):80-86.
[34] Jang SE,Hyam SR,Han MJ,et al. 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]. J Applied Microbiol,2013,115(3):888-896.
[35]曾庆,何肖龙,肖汉森,等.鼠李糖乳杆菌培养上清液通过抑制NF-κB通路预防大肠杆菌性脑膜炎[J].南方医科大学学报,2017,37(1):24-29.Zeng Q,He XL,Xiao HS,et al. Prevention of Escherichia coli meningitis by inhibiting NF-κB pathway in culture supernatant of Lactobacillus rhamnosus[J]. J Southern Med Univ,2017,37(1):24-29.
[36] Pagie S,Gérard N,Charreau B,et al. Notch signaling triggered via the ligand DLL4 impedes M2 macrophage differentiation and promotes their apoptosis[J]. Cell Commun Signal,2018,16(1):4-8.
[37]赵洪伟,车楠,黄超,等. Notch1信号激活核因子κB(NF-κB)参与小鼠RAW264. 7巨噬细胞炎症介质释放[J].细胞与分子免疫学杂志,2017,(10):1310-1315.Zhao HW,Che N,Huang C,et al. Notch1 signaling activates nuclear factor-kappa B(NF-κB)involved in the release of inflammatory mediators in mouse RAW264. 7 macrophages[J]. J Cell Mol Immunol,2017,(10):1310-1315.
[38] Yang GY,Yu J,Su JH,et al. Oral Administration of lactobacillus rhamnosusGG ameliorates salmonella infantis-induced inflammation in a pig model via activation of the IL-22BP/IL-22/STAT3 pathway[J]. Front Cell Infect Microbiol,2017,7:323-356.
[2] Wang N,Liang H,Ke Z. Molecular mechanisms that influence the macrophage M1-M2 polarization balance[J]. Front Immunol,2014,5:614.
[3] Tassiulas I,Parkmin K H,Hu Y,et al. Apoptotic cells inhibit LPSinduced cytokine and chemokine production and IFN responses in macrophages[J]. Human Immunology,2007,68.
[4] Wang Y,Lin YX,Qiao SL,et al. Polymeric nanoparticles promote macrophage reversal from M2 to M1 phenotypes in the tumor microenvironment[J]. Biomaterials,2017,112:153-163.
[5] Wijesundera KK,Izawa T,Tennakoon AH,et al. M1-and M2-macrophage polarization in rat liver cirrhosis induced by thioacetamide(TAA),focusing on Iba1 and galectin-3[J]. Exp Mol Pathol,2014,96(3):382-396.
[6]郑新,王红艳. M2型巨噬细胞极化及相关疾病的研究进展[J].生命科学,2017,29(9):73-80.Zheng X,Wang HY. Research progress of M2 macrophage polarization and related diseases[J]. Life Sci,2017,29(9):73-80.
[7]靳丽媛,司艺玲,陈光辉.巨噬细胞表型极化在糖尿病心肌病发生发展和修复过程中的作用[J].解放军医学院学报,2017,38(1):68-70.Jin LY,Si YL,Chen GH. The role of macrophage phenotypic polarization in the development and repair of diabetic cardiomyopathy[J]. J PLA Univ Med Sci,2017,38(1):68-70.
[8] Wynn TA,Chawla A, Pollard JW. Macrophage biology in development,homeostasis and disease[J]. Nature,2013,496(7446):445-455.
[9] Luo F,Sun X,Qu Z,et al. Salmonella typhimurium-induced M1macrophage polarization is dependent on the bacterial O antigen[J]. World J Microbiol Biotechnol,2016,32(2):22-29.
[10] Chen S,Lu Z,Wang F,et al. Cathelicidin-WA polarizes E. coli K88-induced M1 macrophage to M2-like macrophage in RAW264. 7 cells[J]. Int Immunopharmacol,2017,54:52-64.
[11] Galdiero MR,Mantovani A. Macrophage plasticity and polarization[J]. J Clin Invest,2015,122(3):117-130.
[12] Yalcin AD,Bisgin A,Gorczynski RM. IL-8,IL-10,TGF-β,and GCSF levels were increased in severe persistent allergic asthma patients with the Anti-IgE treatment[J]. Mediat Inflamm,2012,2012(5):720-976.
[13] Page C,Goicochea L,Matthews K,et al. Induction of alternatively activated macrophages enhances pathogenesis during severe acute respiratory syndrome coronavirus infection.[J]. J Virol,2012,86(24):33-34.
[14] Reinartz S,Schumann T,Finkernagel F,et al. Mixed-polarization phenotype of ascites-associated macrophages in human ovarian carcinoma:Correlation of CD163 expression,cytokine levels and early relapse[J]. Int J Cancer,2014,134(1):32-42.
[15] Kong L,Zhang Q,Chao J,et al. Polarization of macrophages induced by Toxoplasma gondii and its impact on abnormal pregnancy in rats[J]. Acta Tropica,2015,143:1-7.
[16]刘勇,徐飞,管俊昌,等.金黄色葡萄球菌及其L型诱导小鼠腹腔巨噬细胞凋亡研究[J].中国人兽共患病学报,2005,21(8):735-735.Liu Y,Xu F,Guan JC,et al. Study on apoptosis of mouse peritoneal macrophages induced by Staphylococcus aureus and its L-type[J]. Chin J Zoonoses,2005,21(8):735-735.
[17]刘东方,薛梅,桑建,等.高黏附性乳酸菌的筛选及其对免疫细胞活性影响的研究[J].中国微生态学杂志,2016,28(8):869-874.Liu DF,Xue M,Sang J,et al. Screening of high adhesion lactic acid bacteria and its effect on immune cell activity[J]. Chin J Microecol,2016,28(8):869-874.
[18]刘红梅,李苏楠,吴婷婷,等. IL-21对LPS诱导的巨噬细胞中细胞因子IL-1β、IL-10、IL-12 mRNA表达的影响[J].中国兽医学报,2014,34(10):1653-1656.Liu HM,Li SN,Wu TT,et al. Effects of IL-21 on the expression of cytokines IL-1β,IL-10 and IL-12 mRNA in LPS-induced macrophages[J]. Chin J Vet Sci,2014,34(10):1653-1656.
[19]廖瑾莉,熊艳,刘志豪,等.慢性华支睾吸虫感染极化M2型巨噬细胞对脓毒症大鼠肺脏保护作用的研究[J].中华急诊医学杂志,2017,26(5):5-33.Liao XL,Xiong Y,Liu ZH,et al. Study on the protective effect of polarized M2 macrophages from chronic clonorchiasis on lung in septic rats[J]. Chin J Emerg Med,2017,26(5):5-33.
[20] Maghsood F,Mirshafiey A,Farahani MM,et al. Dual effects of cell free supernatants from lactobacillus acidophilus and lactobacillus rhamnosu SGG in regulation of MMP-9 by upregulating TIMP-1 and down-regulating CD147 in PMAdifferentiated THP-1 cells[J]. Cell J,2018,19(4):559-568.
[21] Wang J,Fang XB, Wu W. Immunomodulatory effects of Lactobacillus plantarum JLK0142 extracellular polysaccharide on RAW264. 7 macrophages and immunosuppressive mice[J]. Acta Microbiologica Sinica,2018:1-18.
[22] Ichikawa S,Fujii R,Fujiwara D,et al. My D88 but Not TLR2,4 or9 is essential for IL-12 induction by lactic acid bacteria[J].Biosci Biotechnol Biochem,2007,71(12):3026-3032.
[23] Christoffersen TE,Hult LT,Kuczkowska K,et al. In vitro comparison of the effects of probiotic,commensal and pathogenic strains on macrophage polarization[J]. Probiotics Antimicro,2014,6(1):1-10.
[24] Sohn W,Jun DW,Lee KN,et al. Lactobacillus paracasei induces M2-dominant kupffer cell polarization in a mouse model of nonalcoholic steatohepatitis[J]. Digest Dis Sci,2015,60(11):3340-3350.
[25] Ji J,Hu SL,Cui ZW,et al. Probiotic Bacillus amyloliquefaciens mediate M1 macrophage polarization in mouse bone marrowderived macrophages[J]. Arch Microbiol,2013,195(5):349-356.
[26] Saliba A E,Li L,Westermann A J,et al. Single-cell RNA-seq ties macrophage polarization to growth rate of intracellular Salmonella[J]. J Public Health Med,2016,19(4):380-397.
[27] Lo CS,Reverberi D,Balbi C,et al. Mesenchymal stem cellderived extracellular vesicles as mediators of anti-inflammatory effects:endorsement of macrophage polarization[J]. Stem Cells Translat Med,2017,6(3):1018-1028.
[28] Grote K,Schuett J,Schuett H,et al. Toll-like receptors in angiogenesis[J]. Sci World J,2017,11(1):981-991.
[29] Chen K,Xiang Y,Yao X,et al. The active contribution of Tolllike receptors to allergic airway inflammation[J]. Int Immunopharmacol,2011,11(10):1391-1398.
[30]张英春,马微,易华西,等.副干酪乳杆菌M5-L抑制宋内志贺氏菌黏附作用影响因素的研究[J].食品工业科技,2012,33(24):99-102.Zhang YC,Ma W,Yi HX,et al. Study on the factors influencing the adhesion of Lactobacillus paracasei M5-L to Shigella sinensis[J]. Food Sci Techol,2012,33(24):99-102.
[31] Shen CY,Zhang WL,Jiang JG. Immune-enhancing activity of polysaccharides from Hibiscus sabdariffa Linn. via MAPK and NF-κB signaling pathways in RAW264. 7 cells[J]. J Funct Foods,2017,34:118-129.
[32]石少华,王春凤. NF-κB信号传导通路在乳酸菌免疫调节中的作用[J].吉林农业大学学报,2012,34(5):566-570.Shi SH,Wang CF. The role of NF-κB signaling pathway in immune regulation of lactic acid bacteria[J]. J Jilin Agricultural Univ,2012,34(5):566-570.
[33]许光勇,苏敬良,姜金奇,等.乳酸调控大鼠肠黏膜微血管内皮细胞的NF-κB信号通路[J].中国实验动物学报,2012,20(4):80-86.Xu GY,Su JL,Jiang JQ,et al. Regulation of NF-κB signaling pathway in rat intestinal mucosal microvascular endothelial cells by lactic acid[J]. Chin J Exp Animal,2012,20(4):80-86.
[34] Jang SE,Hyam SR,Han MJ,et al. 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]. J Applied Microbiol,2013,115(3):888-896.
[35]曾庆,何肖龙,肖汉森,等.鼠李糖乳杆菌培养上清液通过抑制NF-κB通路预防大肠杆菌性脑膜炎[J].南方医科大学学报,2017,37(1):24-29.Zeng Q,He XL,Xiao HS,et al. Prevention of Escherichia coli meningitis by inhibiting NF-κB pathway in culture supernatant of Lactobacillus rhamnosus[J]. J Southern Med Univ,2017,37(1):24-29.
[36] Pagie S,Gérard N,Charreau B,et al. Notch signaling triggered via the ligand DLL4 impedes M2 macrophage differentiation and promotes their apoptosis[J]. Cell Commun Signal,2018,16(1):4-8.
[37]赵洪伟,车楠,黄超,等. Notch1信号激活核因子κB(NF-κB)参与小鼠RAW264. 7巨噬细胞炎症介质释放[J].细胞与分子免疫学杂志,2017,(10):1310-1315.Zhao HW,Che N,Huang C,et al. Notch1 signaling activates nuclear factor-kappa B(NF-κB)involved in the release of inflammatory mediators in mouse RAW264. 7 macrophages[J]. J Cell Mol Immunol,2017,(10):1310-1315.
[38] Yang GY,Yu J,Su JH,et al. Oral Administration of lactobacillus rhamnosusGG ameliorates salmonella infantis-induced inflammation in a pig model via activation of the IL-22BP/IL-22/STAT3 pathway[J]. Front Cell Infect Microbiol,2017,7:323-356.