微量元素锌的营养免疫作用研究进展
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摘要
锌是生命必需的微量元素,参与到DNA的复制、转录、细胞的增殖、分化、凋亡与信号传导等方面的功能调控。不仅动物必需锌,微生物包括有害微生物也必需锌。然而,过量的锌由于破坏正常的生理代谢具有细胞毒性。因此,哺乳动物已经进化出了错综复杂的机制来调控自身的锌稳态,从整体、细胞水平维持锌的适宜浓度,机体锌的稳态调控由锌感应器、金属硫蛋白与锌转运蛋白等介导。微生物感染时,宿主通过调控锌吸收、降低血液锌浓度,提高肝脏等组织锌浓度,降低细胞中游离锌浓度,从而隔离锌,限制病原微生物对锌的利用,发挥"营养免疫"作用。中性粒细胞分泌的钙卫蛋白在锌营养免疫作用中发挥重要作用。用沙门氏菌感染肉鸡证实存在锌营养免疫作用。本文将综述最近几年在病原微生物感染时,宿主限制病原微生物入侵的新策略以及病原微生物抵抗宿主锌营养免疫的新对策,为完善锌抗病营养理论提供依据。
引文
[1]Vallee B L,Falchuk K H.The biochemical basis of zinc physiology[J].Physiol Rev,1993,73:79-118.
[2]Kirchgessner M,Roth H P,Spoerl R,et al..A comparative view on trace elements and growth[J].Nutr Metab,1977,21:119-143.
[3]Murakami M,Hirano T,Intracellular zinc homeostasis and zinc signaling[J],Cancer Sci,2008,99:1515-1522.
[4]Wastney M E,Aamodt R L,Rumble W F,et al..Kinetic analysis of zinc metabolism and its regulation in normal humans[J].Am J Physiol,1986,251:R398-408.
[5]August D,Janghorbani M,Young V R.Determination of zinc and copper absorption at three dietary Zn-Cu ratios by using stable isotope methods in young adult and elderly subjects[J],Am J Clin Nutr,1989,50:1457-1463.
[6]Nies D H.Biochemistry.How cells control zinc homeostasis[J].Science,2007,317:1695-1696.
[7]Laity J H,Andrews G K.Understanding the mechanisms of zinc-sensing by metal-response element binding transcription factor-1(MTF-1)[J].Arch Biochem Biophys,2007,463:201-210.
[8]Krezel A,Maret W.Thionein/metallothionein control Zn(II)availability and the activity of enzymes[J],J Biol Inorg Chem,2008,13:401-409.
[9]Fernando L P,Wei D Y,Andrews G K.Structure and expression of chicken metallothionein[J].J Nutr,1989,119:309-318.
[10]黄艳玲,罗绪刚,等.饲粮锌对肉鸡生长性能、组织含锌酶活性以及金属硫蛋白含量的影响[J].中国畜牧杂志,2008,44:22-24.
[11]Costas J.Comment on"current understanding of ZIP and ZnT zinc transporters in human health and diseases"[J].Cell Mol Life Sci,2015,72:197-198.
[12]于昱.不同形态锌在肉仔鸡小肠中的吸收特点及机理研究[M].博士学位论文.北京:中国农业科学院,2008.
[13]Shi L,Zhang L,Li C,et al..Dietary zinc deficiency impairs humoral and cellular immune responses to BCG and ESAT-6/CFP-10 vaccination in offspring and adult rats[J].Tuberculosis(Edinb),2016,97:86-96.
[14]Overbeck S,Uciechowski P,Ackland ML.et al..Intracellular zinc homeostasis in leukocyte subsets is regulated by different expression of zinc exporters ZnT-1 to ZnT-9[J].J Leukoc Biol,2008,83:368-380.
[15]Scott M E,Koski K G.Zinc deficiency impairs immune responses against parasitic nematode infections at intestinal and systemic sites[J].J Nutr,2000,130:1412S-1420S.
[16]Prasad A S.Impact of the discovery of human zinc deficiency on health[J].J Trace Elem Med Biol,2014,28:357-363.
[17]Shankar A H,Prasad A S.Zinc and immune function:the biological basis of altered resistance to infection[J].Am J Clin Nutr,1998,68:447S-463S.
[18]Sugiura T,Kuroda E,Yamashita U.Dysfunction of macrophages in metallothionein-knock out mice[J].J UOEH,2004,26:193-205.
[19]Haase H,Rink L.Signal transduction in monocytes:the role of zinc ions[J].Biometals,2007,20:579-585.
[20]Haase H,Ober-Blobaum J L,Engelhardt G,et al..Zinc signals are essential for lipopolysaccharide-induced signal transduction in monocytes[J].J Immunol,2008,181:6491-6502.
[21]Kitamura H,Morikawa H,Kamon H,et al..Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function[J].Nat Immunol,2006,7:971-977.
[22]Prasad A S,Bao B,Beck F W,et al..Zinc-suppressed inflammatory cytokines by induction of A20-mediated inhibition of nuclear factor-kappaB[J].Nutrition,2011,27:816-823.
[23]Breckpot K,Aerts-Toegaert C,Heirman Cet al..Attenuated expression of A20 markedly increases the efficacy of double-stranded RNA-activated dendritic cells as an anti-cancer vaccine[J].J Immunol,2009,182:860-870.
[24]Prasad A S.Clinical,immunological,anti-inflammatory and antioxidant roles of zinc[J].Exp Gerontol,2008,43:370-377.
[25]Li F,Cong T,Li Z,Zhao L.Effects of zinc deficiency on the relevant immune function in rats with sepsis induced by endotoxin/lipopolysaccharide[J].Zhonghua Shao Shang Za Zhi,2015,31:361-366.
[26]Honscheid A,Rink L,Haase H.T-lymphocytes:a target for stimulatory and inhibitory effects of zinc ions[J].Endocr Metab Immune Disord Drug Targets,2009,9:132-144.
[27]Prasad A S.Effects of zinc deficiency on Thl and Th2 cytokine shifts[J].J Infect Dis,2000,182 Suppl l:S62-68.
[28]Fraker P J,King L E.Reprogramming of the immune system during zinc deficiency[J],Annu Rev Nutr,2004,24:277-298.
[29]Hojyo S,Miyai T,Fujishiro H,et al..Zinc transporter SLC39A10/ZIP10 controls humoral immunity by modulating B-cell receptor signal strength[J].Proc Natl Acad Sci USA,2014,111:11786-11791.
[30]Miyai T,Hojyo S,Ikawa T,et al..Zinc transporter SLC39A10/ZIP10 facilitates antiapoptotic signaling during early B-cell development[J].Proc Natl Acad Sci USA,2014,111:11780-11785.
[31]Paganelli R,Quinti I,Fagiolo U,et al..Changes in circulating B cells and immunoglobulin classes and subclasses in a healthy aged population[J].Clin Exp Immunol,1992,90:351-354.
[32]Cook-Mills J M,Fraker P J.Functional capacity of the residual lymphocytes from zinc-deficient adult mice[J].Br J Nutr,1993,69:835-848.
[33]King L E,Frentzel J W,Mann J J,et al..Chronic zinc deficiency in mice disrupted T cell lymphopoiesis and erythropoiesis while B cell lymphopoiesis and myelopoiesis were maintained[J].J Am Coll Nutr,2005,24:494-502.
[34]Waldron K J,Robinson N J.How do bacterial cells ensure that metalloproteins get the correct metal?[J].Nat Rev Microbiol,2009,7:25-35.
[35]Liu J Z,Jellbauer S,Poe A J,et al..Zinc sequestration by the neutrophil protein calprotectin enhances Salmonella growth in the inflamed gut[J].Cell Host Microbe,2012,11:227-239.
[36]Subramanian Vignesh K,Landero Figueroa J A,Porollo A,et al..Granulocyte macrophage-colony stimulating factor induced Zn sequestration enhances macrophage superoxide and limits intracellular pathogen survival[J].Immunity,2013,39:697-710.
[37]Porcheron G,Garenaux A,Proulx],et al..Iron,copper,zinc,and manganese transport and regulation in pathogenic Enterobacteria:correlations between strains,site of infection and the relative importance of the different metal transport systems for virulence[J].Front Cell Infect Microbiol,2013,3:90.
[38]Liuzzi J P,Lichten L A,Rivera S,et al..Interleukin-6 regulates the zinc transporter Zipl4 in liver and contributes to the hypozincemia of the acute-phase response[J].Proc Natl Acad Sci USA,2005,102:6843-6848.
[39]Glaser R,Harder J,Lange H,et al..Antimicrobial psoriasin(S100A7)protects human skin from Escherichia coli infection[J].Nat Immunol,2005,6:57-64.
[40]Mildner M,Stichenwirth M,Abtin A,et al..Psoriasin(S100A7)is a major Escherichia coli-cidal factor of the female genital tract[J].Mucosal Immunol,2010,3:602-609.
[41]Morgan M R,Jazayeri M,Ramsay A G,et al..Psoriasin(S100A7)associates with integrin beta6 subunit and is required for alphavbeta6-dependent carcinoma cell invasion[J].Oncogene,2011,30:1422-1435.
[42]Moroz O V,Burkitt W,Wittkowski H,et al..Both Ca~(2+)and Zn~(2+)are essential for S100A12 protein oligomerization and function[J].BMC Biochem,2009,10:11.
[43]Pietzsch J,Hoppmann S.Human S100A12:a novel key player in inflammation?[J].Amino Acids,2009,36:381-389.
[44]Gebhardt C,Nemeth J,Angel P.et al..S100A8 and S100A9 in inflammation and cancer[J].Biochem Pharmacol,2006,72:1622-1631.
[45]Kehl-Fie T E,Chitayat S,Hood MI,et al..Nutrient metal sequestration by calprotectin inhibits bacterial superoxide defense,enhancing neutrophil killing of Staphylococcus aureus[J].Cell Host Microbe,2011,10:158-164.
[46]Brophy M B,Hayden J A,Nolan E M.Calcium ion gradients modulate the zinc affinity and antibacterial activity of human calprotectin[J].J Am Chem Soc,2012,134:18089-18100.
[47]Damo S M,Kehl-Fie T E,Sugitani N,et al..Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens[J].Proc Natl Acad Sci USA,2013,110:3841-3846.
[48]Corbin B D,Seeley E H,Raab A,et al..Metal chelation and inhibition of bacterial growth in tissue abscesses[J].Science,2008,319:962-965.
[49]Amich J,Vicentefranqueira R,Mellado E,et al..The ZrfC alkaline zinc transporter is required for Aspergillus fumigatus virulence and its growth in the presence of the Zn/Mn-chelating protein calprotectin[J].Cell Microbiol,2014,16:548-564.
[50]Becker K W,Skaar E P.Metal limitation and toxicity at the interface between host and pathogen[J].FEMS Microbiol Rev,2014,38:1235-1249.
[51]Botella H,Peyron P,Levillain F,et al..Mycobacterial p(1)-type ATPases mediate resistance to zinc poisoning in human macrophages[J],Cell Host Microbe,2011,10:248-259.
[52]Wang D,Hosteen O,Fierke CA.ZntR-mediated transcription of zntA responds to nanomolar intracellular free zinc[J].J Inorg Biochem,2012,111:173-181.
[53]Rensing C,Mitra B,Rosen B P.The zntA gene of Escherichia coli encodes a ZnCIDtranslocating P-type ATPase[J].Proc Natl Acad Sci USA,1997,94:14326-14331.
[54]Grass G,Fan B,Rosen B P,et al..ZitB(YbgR),a member of the cation diffusion facilitator family,is an additional zinc transporter in Escherichia coli[J].J Bacterid,2001,183:4664-4667.
[55]Klein J S,Lewinson O.Bacterial ATP-driven transporters of transition metals:physiological roles,mechanisms of action,and roles in bacterial virulence.Metallomics,2011,3:1098-1108.
[56]Godinez I,Raffatellu M,Chu H,et al..Interleukin-23 orchestrates mucosal responses to Salmonella enterica serotype Typhimurium in the intestine[J].Infect Immun,2009,77:387-398.
[57]Zhang B,Shao Y,Liu D,et al..Zinc prevents Salmonella enterica serovar Typhimurium-induced loss of intestinal mucosal barrier function in broiler chickens[J].Avian Pathol,2012,41:361-367.
[58]邵玉新,张炳坤.日粮中添加锌对鼠伤寒沙门氏菌感染肉仔鸡生产性能和肠道微生物区系的影响[M].中国畜牧兽医学会动物营养学分会第十一次全国动物营养学术研讨会论文集,2012.
[59]成廷水.氨基酸锌对蛋鸡免疫和抗氧化功能的调节作用及其应用研究[M].博士学位论文.北京:中国农业大学,2004.
[60]Troche.The impact of zinc on croeth and barrier function during administration a coccidial vaccine[M].Purdue University,2012.
[61]伍爱民.锌转运蛋白Zip11的功能及沙门氏菌攻击对肉鸡锌稳态的影响及调控机理研究[M].博士学位论文.成都:四川农业大学,2016.
[2]Kirchgessner M,Roth H P,Spoerl R,et al..A comparative view on trace elements and growth[J].Nutr Metab,1977,21:119-143.
[3]Murakami M,Hirano T,Intracellular zinc homeostasis and zinc signaling[J],Cancer Sci,2008,99:1515-1522.
[4]Wastney M E,Aamodt R L,Rumble W F,et al..Kinetic analysis of zinc metabolism and its regulation in normal humans[J].Am J Physiol,1986,251:R398-408.
[5]August D,Janghorbani M,Young V R.Determination of zinc and copper absorption at three dietary Zn-Cu ratios by using stable isotope methods in young adult and elderly subjects[J],Am J Clin Nutr,1989,50:1457-1463.
[6]Nies D H.Biochemistry.How cells control zinc homeostasis[J].Science,2007,317:1695-1696.
[7]Laity J H,Andrews G K.Understanding the mechanisms of zinc-sensing by metal-response element binding transcription factor-1(MTF-1)[J].Arch Biochem Biophys,2007,463:201-210.
[8]Krezel A,Maret W.Thionein/metallothionein control Zn(II)availability and the activity of enzymes[J],J Biol Inorg Chem,2008,13:401-409.
[9]Fernando L P,Wei D Y,Andrews G K.Structure and expression of chicken metallothionein[J].J Nutr,1989,119:309-318.
[10]黄艳玲,罗绪刚,等.饲粮锌对肉鸡生长性能、组织含锌酶活性以及金属硫蛋白含量的影响[J].中国畜牧杂志,2008,44:22-24.
[11]Costas J.Comment on"current understanding of ZIP and ZnT zinc transporters in human health and diseases"[J].Cell Mol Life Sci,2015,72:197-198.
[12]于昱.不同形态锌在肉仔鸡小肠中的吸收特点及机理研究[M].博士学位论文.北京:中国农业科学院,2008.
[13]Shi L,Zhang L,Li C,et al..Dietary zinc deficiency impairs humoral and cellular immune responses to BCG and ESAT-6/CFP-10 vaccination in offspring and adult rats[J].Tuberculosis(Edinb),2016,97:86-96.
[14]Overbeck S,Uciechowski P,Ackland ML.et al..Intracellular zinc homeostasis in leukocyte subsets is regulated by different expression of zinc exporters ZnT-1 to ZnT-9[J].J Leukoc Biol,2008,83:368-380.
[15]Scott M E,Koski K G.Zinc deficiency impairs immune responses against parasitic nematode infections at intestinal and systemic sites[J].J Nutr,2000,130:1412S-1420S.
[16]Prasad A S.Impact of the discovery of human zinc deficiency on health[J].J Trace Elem Med Biol,2014,28:357-363.
[17]Shankar A H,Prasad A S.Zinc and immune function:the biological basis of altered resistance to infection[J].Am J Clin Nutr,1998,68:447S-463S.
[18]Sugiura T,Kuroda E,Yamashita U.Dysfunction of macrophages in metallothionein-knock out mice[J].J UOEH,2004,26:193-205.
[19]Haase H,Rink L.Signal transduction in monocytes:the role of zinc ions[J].Biometals,2007,20:579-585.
[20]Haase H,Ober-Blobaum J L,Engelhardt G,et al..Zinc signals are essential for lipopolysaccharide-induced signal transduction in monocytes[J].J Immunol,2008,181:6491-6502.
[21]Kitamura H,Morikawa H,Kamon H,et al..Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function[J].Nat Immunol,2006,7:971-977.
[22]Prasad A S,Bao B,Beck F W,et al..Zinc-suppressed inflammatory cytokines by induction of A20-mediated inhibition of nuclear factor-kappaB[J].Nutrition,2011,27:816-823.
[23]Breckpot K,Aerts-Toegaert C,Heirman Cet al..Attenuated expression of A20 markedly increases the efficacy of double-stranded RNA-activated dendritic cells as an anti-cancer vaccine[J].J Immunol,2009,182:860-870.
[24]Prasad A S.Clinical,immunological,anti-inflammatory and antioxidant roles of zinc[J].Exp Gerontol,2008,43:370-377.
[25]Li F,Cong T,Li Z,Zhao L.Effects of zinc deficiency on the relevant immune function in rats with sepsis induced by endotoxin/lipopolysaccharide[J].Zhonghua Shao Shang Za Zhi,2015,31:361-366.
[26]Honscheid A,Rink L,Haase H.T-lymphocytes:a target for stimulatory and inhibitory effects of zinc ions[J].Endocr Metab Immune Disord Drug Targets,2009,9:132-144.
[27]Prasad A S.Effects of zinc deficiency on Thl and Th2 cytokine shifts[J].J Infect Dis,2000,182 Suppl l:S62-68.
[28]Fraker P J,King L E.Reprogramming of the immune system during zinc deficiency[J],Annu Rev Nutr,2004,24:277-298.
[29]Hojyo S,Miyai T,Fujishiro H,et al..Zinc transporter SLC39A10/ZIP10 controls humoral immunity by modulating B-cell receptor signal strength[J].Proc Natl Acad Sci USA,2014,111:11786-11791.
[30]Miyai T,Hojyo S,Ikawa T,et al..Zinc transporter SLC39A10/ZIP10 facilitates antiapoptotic signaling during early B-cell development[J].Proc Natl Acad Sci USA,2014,111:11780-11785.
[31]Paganelli R,Quinti I,Fagiolo U,et al..Changes in circulating B cells and immunoglobulin classes and subclasses in a healthy aged population[J].Clin Exp Immunol,1992,90:351-354.
[32]Cook-Mills J M,Fraker P J.Functional capacity of the residual lymphocytes from zinc-deficient adult mice[J].Br J Nutr,1993,69:835-848.
[33]King L E,Frentzel J W,Mann J J,et al..Chronic zinc deficiency in mice disrupted T cell lymphopoiesis and erythropoiesis while B cell lymphopoiesis and myelopoiesis were maintained[J].J Am Coll Nutr,2005,24:494-502.
[34]Waldron K J,Robinson N J.How do bacterial cells ensure that metalloproteins get the correct metal?[J].Nat Rev Microbiol,2009,7:25-35.
[35]Liu J Z,Jellbauer S,Poe A J,et al..Zinc sequestration by the neutrophil protein calprotectin enhances Salmonella growth in the inflamed gut[J].Cell Host Microbe,2012,11:227-239.
[36]Subramanian Vignesh K,Landero Figueroa J A,Porollo A,et al..Granulocyte macrophage-colony stimulating factor induced Zn sequestration enhances macrophage superoxide and limits intracellular pathogen survival[J].Immunity,2013,39:697-710.
[37]Porcheron G,Garenaux A,Proulx],et al..Iron,copper,zinc,and manganese transport and regulation in pathogenic Enterobacteria:correlations between strains,site of infection and the relative importance of the different metal transport systems for virulence[J].Front Cell Infect Microbiol,2013,3:90.
[38]Liuzzi J P,Lichten L A,Rivera S,et al..Interleukin-6 regulates the zinc transporter Zipl4 in liver and contributes to the hypozincemia of the acute-phase response[J].Proc Natl Acad Sci USA,2005,102:6843-6848.
[39]Glaser R,Harder J,Lange H,et al..Antimicrobial psoriasin(S100A7)protects human skin from Escherichia coli infection[J].Nat Immunol,2005,6:57-64.
[40]Mildner M,Stichenwirth M,Abtin A,et al..Psoriasin(S100A7)is a major Escherichia coli-cidal factor of the female genital tract[J].Mucosal Immunol,2010,3:602-609.
[41]Morgan M R,Jazayeri M,Ramsay A G,et al..Psoriasin(S100A7)associates with integrin beta6 subunit and is required for alphavbeta6-dependent carcinoma cell invasion[J].Oncogene,2011,30:1422-1435.
[42]Moroz O V,Burkitt W,Wittkowski H,et al..Both Ca~(2+)and Zn~(2+)are essential for S100A12 protein oligomerization and function[J].BMC Biochem,2009,10:11.
[43]Pietzsch J,Hoppmann S.Human S100A12:a novel key player in inflammation?[J].Amino Acids,2009,36:381-389.
[44]Gebhardt C,Nemeth J,Angel P.et al..S100A8 and S100A9 in inflammation and cancer[J].Biochem Pharmacol,2006,72:1622-1631.
[45]Kehl-Fie T E,Chitayat S,Hood MI,et al..Nutrient metal sequestration by calprotectin inhibits bacterial superoxide defense,enhancing neutrophil killing of Staphylococcus aureus[J].Cell Host Microbe,2011,10:158-164.
[46]Brophy M B,Hayden J A,Nolan E M.Calcium ion gradients modulate the zinc affinity and antibacterial activity of human calprotectin[J].J Am Chem Soc,2012,134:18089-18100.
[47]Damo S M,Kehl-Fie T E,Sugitani N,et al..Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens[J].Proc Natl Acad Sci USA,2013,110:3841-3846.
[48]Corbin B D,Seeley E H,Raab A,et al..Metal chelation and inhibition of bacterial growth in tissue abscesses[J].Science,2008,319:962-965.
[49]Amich J,Vicentefranqueira R,Mellado E,et al..The ZrfC alkaline zinc transporter is required for Aspergillus fumigatus virulence and its growth in the presence of the Zn/Mn-chelating protein calprotectin[J].Cell Microbiol,2014,16:548-564.
[50]Becker K W,Skaar E P.Metal limitation and toxicity at the interface between host and pathogen[J].FEMS Microbiol Rev,2014,38:1235-1249.
[51]Botella H,Peyron P,Levillain F,et al..Mycobacterial p(1)-type ATPases mediate resistance to zinc poisoning in human macrophages[J],Cell Host Microbe,2011,10:248-259.
[52]Wang D,Hosteen O,Fierke CA.ZntR-mediated transcription of zntA responds to nanomolar intracellular free zinc[J].J Inorg Biochem,2012,111:173-181.
[53]Rensing C,Mitra B,Rosen B P.The zntA gene of Escherichia coli encodes a ZnCIDtranslocating P-type ATPase[J].Proc Natl Acad Sci USA,1997,94:14326-14331.
[54]Grass G,Fan B,Rosen B P,et al..ZitB(YbgR),a member of the cation diffusion facilitator family,is an additional zinc transporter in Escherichia coli[J].J Bacterid,2001,183:4664-4667.
[55]Klein J S,Lewinson O.Bacterial ATP-driven transporters of transition metals:physiological roles,mechanisms of action,and roles in bacterial virulence.Metallomics,2011,3:1098-1108.
[56]Godinez I,Raffatellu M,Chu H,et al..Interleukin-23 orchestrates mucosal responses to Salmonella enterica serotype Typhimurium in the intestine[J].Infect Immun,2009,77:387-398.
[57]Zhang B,Shao Y,Liu D,et al..Zinc prevents Salmonella enterica serovar Typhimurium-induced loss of intestinal mucosal barrier function in broiler chickens[J].Avian Pathol,2012,41:361-367.
[58]邵玉新,张炳坤.日粮中添加锌对鼠伤寒沙门氏菌感染肉仔鸡生产性能和肠道微生物区系的影响[M].中国畜牧兽医学会动物营养学分会第十一次全国动物营养学术研讨会论文集,2012.
[59]成廷水.氨基酸锌对蛋鸡免疫和抗氧化功能的调节作用及其应用研究[M].博士学位论文.北京:中国农业大学,2004.
[60]Troche.The impact of zinc on croeth and barrier function during administration a coccidial vaccine[M].Purdue University,2012.
[61]伍爱民.锌转运蛋白Zip11的功能及沙门氏菌攻击对肉鸡锌稳态的影响及调控机理研究[M].博士学位论文.成都:四川农业大学,2016.