巨噬细胞凋亡抗结核分枝杆菌感染的研究进展
摘要
结核分枝杆菌(MTB)是结核病病原体,长期协同进化使得MTB制定出专门的免疫逃逸机制。巨噬细胞凋亡作为机体抗感染固有免疫应答之一,能有效清除胞内MTB。我们主要总结了MTB与巨噬细胞凋亡相互作用:巨噬细胞主要通过内在途径及宿主蛋白核小体蛋白110(SP110)、磷酸化的信号转导子和转录激活子(STAT)、非编码RNA(ncRNA)介导细胞凋亡从而控制MTB感染; MTB脯-谷氨酸/脯-脯-谷氨酸(PE/PPE)家族蛋白、毒力因子Rv3033等菌体成分通过多种分子机制调控宿主细胞凋亡,促进自身存活。关于巨噬细胞凋亡抗MTB感染机制的深入研究,将为基于巨噬细胞凋亡的结核病免疫治疗带来新的策略。
引文
[1] 赵润鹏,吴静,胡东.结核分枝杆菌感染的巨噬细胞的死亡和自噬[J].细胞与分子免疫学杂志.2016,32(12):1711-1714.Zhao R,Wu J,Hu D.Death and autophagy of macrophage infected with M.tuberculosis[J].Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi,2016,32(12):1711-1714.
[2] Zhao X,Khan N,Gan H,et al.Bcl-x(L) mediates RIPK3-dependent necrosis in M.tuberculosis-infected macrophages[J].Mucosal Immunol,2017,10(6):1553-1568.
[3] Lee K I,Whang J,Choi H G,et al.Mycobacterium avium MAV2054 protein induces macrophage apoptosis by targeting mitochondria and reduces intracellular bacterial growth[J/OL].Sci Rep,2016,6:37804.DOI:10.1038/srep37804.
[4] Tripathi A,Srivastava V,Singh B N.hsa-let-7b-5p facilitates Mycobacterium tuberculosis survival in THP-1 human macrophages by Fas downregulation[J].FEMS Microbiol Lett,2018,365(7).DOI:10.1093/femsle/fny040.
[5] Joseph S,Yuen A,Singh V,et al.Mycobacterium tuberculosis Cpn60.2 (GroEL2) blocks macrophage apoptosis via interaction with mitochondrial mortalin[J].Biol Open,2017,6(4):481-488.
[6] Saquib N M,Jamwal S,Midha M K,et al.Quantitative proteomics and lipidomics analysis of endoplasmic reticulum of macrophage infected with Mycobacterium tuberculosis[J/OL].Int J Proteomics,2015,2015:270438.DOI:10.1155/2015/270438.Epub 2015 Feb 16.
[7] Lim Y J,Yi M H,Choi J A,et al.Roles of endoplasmic reticulum stress-mediated apoptosis in M1-polarized macrophages during mycobacterial infections[J/OL].Sci Rep,2016,6:37211.DOI:10.1038/srep37211.
[8] Jo S H,Choi J A,Lim Y J,et al.Calreticulin modulates the intracellular survival of mycobacteria by regulating ER-stress-mediated apoptosis[J].Oncotarget,2017,8(35):58686-58698.
[9] Wu Y,Guo Z,Yao K,et al.The transcriptional foundations of Sp110-mediated macrophage (RAW264.7) resistance to Mycobacterium tuberculosis H37Ra[J/OL].Sci Rep,2016,6:22041.DOI:10.1038/srep22041.
[10] Wu Y,Guo Z,Liu F,et al.Sp110 enhances macrophage resistance to Mycobacterium tuberculosis via inducing endoplasmic reticulum stress and inhibiting anti-apoptotic factors[J].Oncotarget,2017,8(38):64050-64065.
[11] Yao K,Chen Q,Wu Y,et al.Unphosphorylated STAT1 represses apoptosis in macrophages during Mycobacterium tuberculosis infection[J].J Cell Sci,2017,130(10):1740-1751.
[12] Shi J,Sun B H,Zhou L R,et al.Role of IL-10 and TNF-alpha during Mycobacterium tuberculosis infection in murine alveolar macrophages[J/OL].Genet Mol Res,2016,15(3).DOI:10.4238/gmr.15037819.
[13] Zhuang Z G,Zhang J A,Luo H L,et al.The circular RNA of peripheral blood mononuclear cells:Hsa_circ_0005836 as a new diagnostic biomarker and therapeutic target of active pulmonary tuberculosis[J].Mol Immunol,2017,90:264-272.
[14] Li M,Cui J,Niu W,et al.Long non-coding PCED1B-AS1 regulates macrophage apoptosis and autophagy by sponging miR-155 in active tuberculosis[J].Biochem Biophys Res Commun,2019,509:803-809.
[15] Abdalla A E,Duan X,Deng W,et al.microRNAs play big roles in modulating macrophages response toward mycobacteria infection[J].Infect Genet Evol,2016,45:378-382.
[16] Zhang D,Yi Z,Fu Y.Downregulation of miR-20b-5p facilitates Mycobacterium tuberculosis survival in RAW 264.7 macrophages via attenuating the cell apoptosis by Mcl-1 upregulation[J].J Cell Biochem,2019,120(4):5889-5896.
[17] Liang S,Song Z,Wu Y,et al.microRNA-27b modulates inflammatory response and apoptosis during Mycobacterium tuberculosis infection[J].J Immunol,2018,200(10):3506-3518.
[18] Zhao Z,Hao J,Li X,et al.miR-21-5p regulates mycobacterial survival and inflammatory responses by targeting Bcl-2 and TLR4 in Mycobacterium tuberculosis-infected macrophages[J].FEBS Lett,2019,593(12):1326-1335.
[19] 邓万燕.结核分枝杆菌PE/PPE家族蛋白的性质及其在与宿主细胞相互作用中的功能 [D].重庆:西南大学,2015.Deng W.The properties of Mycobacterium tuberculosis PE/PPE family proteins and their function in interaction with host cells[D].Chongqing:Southwest University,2015.
[20] Yang W,Deng W,Zeng J,et al.Mycobacterium tuberculosis PE_PGRS18 enhances the intracellular survival of M.smegmatis via altering host macrophage cytokine profiling and attenuating the cell apoptosis[J].Apoptosis,2017,22(4):502-509.
[21] Tiwari B,Ramakrishnan U M,Raghunand T R.The Mycobacterium tuberculosis protein pair PE9 (Rv1088)-PE10 (Rv1089) forms heterodimers and induces macrophage apoptosis through Toll-like receptor 4[J].Cell Microbiol,2015,17(11):1653-1669.
[22] Grover S,Sharma T,Singh Y,et al.The PGRS domain of Mycobacterium tuberculosis PE_PGRS protein Rv0297 is involved in endoplasmic reticulum stress-mediated apoptosis through Toll-like receptor 4[J/OL].MBio,2018,9(3):e01017-18.DOI:10.1128/mBio.01017-18.
[23] Yang S,Li F,Jia S,et al.Early secreted antigen ESAT-6 of Mycobacterium tuberculosis promotes apoptosis of macrophages via targeting the microRNA155-SOCS1 interaction[J].Cell Physiol Biochem,2015,35(4):1276-1288.
[24] Lin J,Chang Q,Dai X,et al.Early secreted antigenic target of 6-kDa of Mycobacterium tuberculosis promotes caspase-9/caspase-3-mediated apoptosis in macrophages[J].Mol Cell Biochem,2019,457(1/2):179-189.
[25] Perkowski E F,Miller B K,McCann J R,et al.An orphaned Mce-associated membrane protein of Mycobacterium tuberculosis is a virulence factor that stabilizes Mce transporters[J].Mol Microbiol,2016,100(1):90-107.
[26] Rodriguez D C,Ocampo M,Varela Y,et al.Mce4F Mycobacterium tuberculosis protein peptides can inhibit invasion of human cell lines[J/OL].Pathog Dis,2015,73(3):ftu020.DOI:10.1093/femspd/ftu020.Epub 2014 Dec 11.
[27] Saini N K,Sinha R,Singh P,et al.Mce4A protein of Mycobacterium tuberculosis induces pro inflammatory cytokine response leading to macrophage apoptosis in a TNF-alpha dependent manner[J].Microb Pathog,2016,100:43-50.
[28] Yan S,Zhen J,Li Y,et al.Mce-associated protein Rv0177 alters the cell wall structure of Mycobacterium smegmatis and promotes macrophage apoptosis via regulating the cytokines[J].Int Immunopharmacol,2019,66:205-214.
[29] Wang L,Zuo M,Chen H,et al.Mycobacterium tuberculosis lipoprotein MPT83 induces apoptosis of infected macrophages by activating the TLR2/p38/COX-2 signaling pathway[J].J Immunol,2017,198(12):4772-4780.
[30] Su H,Zhu S,Zhu L,et al.Recombinant lipoprotein Rv1016c derived from Mycobacterium tuberculosis is a TLR-2 ligand that induces macrophages apoptosis and inhibits MHC II antigen processing[J/OL].Front Cell Infect Microbiol,2016,6:147.DOI:10.3389/fcimb.2016.00147.
[31] Li F,Feng L,Jin C,et al.LpqT improves mycobacteria survival in macrophages by inhibiting TLR2 mediated inflammatory cytokine expression and cell apoptosis[J].Tuberculosis (Edinb),2018,111:57-66.
[32] Zhang W,Lu Q,Dong Y,et al.Rv3033,as an emerging anti-apoptosis factor,facilitates mycobacteria survival via inhibiting macrophage intrinsic apoptosis[J/OL].Front Immunol,2018,9:2136.DOI:10.3389/fimmu.2018.02136.eCollection 2018.
[33] 王士荣.抗结核药物的研究进展[J].内江科技,2018,5:82.Wang S.Progress on anti-tuberculosis drugs[J].Nei Jiang Ke Ji,2018,5:82.
[34] Sharma A,Vaghasiya K,Gupta P,et al.Reclaiming hijacked phagosomes:Hybrid nano-in-micro encapsulated MIAP peptide ensures host directed therapy by specifically augmenting phagosome-maturation and apoptosis in TB infected macrophage cells[J].Int J Pharm,2018,536(1):50-62.
[35] Amarnath Praphakar R,Jeyaraj M,Ahmed M,et al.Silver nanoparticle functionalized CS-g-(CA-MA-PZA) carrier for sustainable anti-tuberculosis drug delivery[J].Int J Biol Macromol,2018,118(Pt B):1627-1638.
[36] Machelart A,Salzano G,Li X,et al.Intrinsic antibacterial activity of nanoparticles made of β-cyclodextrins potentiates their effect as drug nanocarriers against tuberculosis[J].ACS Nano,2019,13(4):3992-4007.
[37] Su H,Zhu S,Zhu L,et al.Mycobacterium tuberculosis latent antigen Rv2029c from the multistage DNA vaccine A39 drives TH1 responses via TLR-mediated macrophage activation[J/OL].Front Microbiol,2017,8:2266.DOI:10.3389/fmicb.2017.02266.eCollection 2017.
[2] Zhao X,Khan N,Gan H,et al.Bcl-x(L) mediates RIPK3-dependent necrosis in M.tuberculosis-infected macrophages[J].Mucosal Immunol,2017,10(6):1553-1568.
[3] Lee K I,Whang J,Choi H G,et al.Mycobacterium avium MAV2054 protein induces macrophage apoptosis by targeting mitochondria and reduces intracellular bacterial growth[J/OL].Sci Rep,2016,6:37804.DOI:10.1038/srep37804.
[4] Tripathi A,Srivastava V,Singh B N.hsa-let-7b-5p facilitates Mycobacterium tuberculosis survival in THP-1 human macrophages by Fas downregulation[J].FEMS Microbiol Lett,2018,365(7).DOI:10.1093/femsle/fny040.
[5] Joseph S,Yuen A,Singh V,et al.Mycobacterium tuberculosis Cpn60.2 (GroEL2) blocks macrophage apoptosis via interaction with mitochondrial mortalin[J].Biol Open,2017,6(4):481-488.
[6] Saquib N M,Jamwal S,Midha M K,et al.Quantitative proteomics and lipidomics analysis of endoplasmic reticulum of macrophage infected with Mycobacterium tuberculosis[J/OL].Int J Proteomics,2015,2015:270438.DOI:10.1155/2015/270438.Epub 2015 Feb 16.
[7] Lim Y J,Yi M H,Choi J A,et al.Roles of endoplasmic reticulum stress-mediated apoptosis in M1-polarized macrophages during mycobacterial infections[J/OL].Sci Rep,2016,6:37211.DOI:10.1038/srep37211.
[8] Jo S H,Choi J A,Lim Y J,et al.Calreticulin modulates the intracellular survival of mycobacteria by regulating ER-stress-mediated apoptosis[J].Oncotarget,2017,8(35):58686-58698.
[9] Wu Y,Guo Z,Yao K,et al.The transcriptional foundations of Sp110-mediated macrophage (RAW264.7) resistance to Mycobacterium tuberculosis H37Ra[J/OL].Sci Rep,2016,6:22041.DOI:10.1038/srep22041.
[10] Wu Y,Guo Z,Liu F,et al.Sp110 enhances macrophage resistance to Mycobacterium tuberculosis via inducing endoplasmic reticulum stress and inhibiting anti-apoptotic factors[J].Oncotarget,2017,8(38):64050-64065.
[11] Yao K,Chen Q,Wu Y,et al.Unphosphorylated STAT1 represses apoptosis in macrophages during Mycobacterium tuberculosis infection[J].J Cell Sci,2017,130(10):1740-1751.
[12] Shi J,Sun B H,Zhou L R,et al.Role of IL-10 and TNF-alpha during Mycobacterium tuberculosis infection in murine alveolar macrophages[J/OL].Genet Mol Res,2016,15(3).DOI:10.4238/gmr.15037819.
[13] Zhuang Z G,Zhang J A,Luo H L,et al.The circular RNA of peripheral blood mononuclear cells:Hsa_circ_0005836 as a new diagnostic biomarker and therapeutic target of active pulmonary tuberculosis[J].Mol Immunol,2017,90:264-272.
[14] Li M,Cui J,Niu W,et al.Long non-coding PCED1B-AS1 regulates macrophage apoptosis and autophagy by sponging miR-155 in active tuberculosis[J].Biochem Biophys Res Commun,2019,509:803-809.
[15] Abdalla A E,Duan X,Deng W,et al.microRNAs play big roles in modulating macrophages response toward mycobacteria infection[J].Infect Genet Evol,2016,45:378-382.
[16] Zhang D,Yi Z,Fu Y.Downregulation of miR-20b-5p facilitates Mycobacterium tuberculosis survival in RAW 264.7 macrophages via attenuating the cell apoptosis by Mcl-1 upregulation[J].J Cell Biochem,2019,120(4):5889-5896.
[17] Liang S,Song Z,Wu Y,et al.microRNA-27b modulates inflammatory response and apoptosis during Mycobacterium tuberculosis infection[J].J Immunol,2018,200(10):3506-3518.
[18] Zhao Z,Hao J,Li X,et al.miR-21-5p regulates mycobacterial survival and inflammatory responses by targeting Bcl-2 and TLR4 in Mycobacterium tuberculosis-infected macrophages[J].FEBS Lett,2019,593(12):1326-1335.
[19] 邓万燕.结核分枝杆菌PE/PPE家族蛋白的性质及其在与宿主细胞相互作用中的功能 [D].重庆:西南大学,2015.Deng W.The properties of Mycobacterium tuberculosis PE/PPE family proteins and their function in interaction with host cells[D].Chongqing:Southwest University,2015.
[20] Yang W,Deng W,Zeng J,et al.Mycobacterium tuberculosis PE_PGRS18 enhances the intracellular survival of M.smegmatis via altering host macrophage cytokine profiling and attenuating the cell apoptosis[J].Apoptosis,2017,22(4):502-509.
[21] Tiwari B,Ramakrishnan U M,Raghunand T R.The Mycobacterium tuberculosis protein pair PE9 (Rv1088)-PE10 (Rv1089) forms heterodimers and induces macrophage apoptosis through Toll-like receptor 4[J].Cell Microbiol,2015,17(11):1653-1669.
[22] Grover S,Sharma T,Singh Y,et al.The PGRS domain of Mycobacterium tuberculosis PE_PGRS protein Rv0297 is involved in endoplasmic reticulum stress-mediated apoptosis through Toll-like receptor 4[J/OL].MBio,2018,9(3):e01017-18.DOI:10.1128/mBio.01017-18.
[23] Yang S,Li F,Jia S,et al.Early secreted antigen ESAT-6 of Mycobacterium tuberculosis promotes apoptosis of macrophages via targeting the microRNA155-SOCS1 interaction[J].Cell Physiol Biochem,2015,35(4):1276-1288.
[24] Lin J,Chang Q,Dai X,et al.Early secreted antigenic target of 6-kDa of Mycobacterium tuberculosis promotes caspase-9/caspase-3-mediated apoptosis in macrophages[J].Mol Cell Biochem,2019,457(1/2):179-189.
[25] Perkowski E F,Miller B K,McCann J R,et al.An orphaned Mce-associated membrane protein of Mycobacterium tuberculosis is a virulence factor that stabilizes Mce transporters[J].Mol Microbiol,2016,100(1):90-107.
[26] Rodriguez D C,Ocampo M,Varela Y,et al.Mce4F Mycobacterium tuberculosis protein peptides can inhibit invasion of human cell lines[J/OL].Pathog Dis,2015,73(3):ftu020.DOI:10.1093/femspd/ftu020.Epub 2014 Dec 11.
[27] Saini N K,Sinha R,Singh P,et al.Mce4A protein of Mycobacterium tuberculosis induces pro inflammatory cytokine response leading to macrophage apoptosis in a TNF-alpha dependent manner[J].Microb Pathog,2016,100:43-50.
[28] Yan S,Zhen J,Li Y,et al.Mce-associated protein Rv0177 alters the cell wall structure of Mycobacterium smegmatis and promotes macrophage apoptosis via regulating the cytokines[J].Int Immunopharmacol,2019,66:205-214.
[29] Wang L,Zuo M,Chen H,et al.Mycobacterium tuberculosis lipoprotein MPT83 induces apoptosis of infected macrophages by activating the TLR2/p38/COX-2 signaling pathway[J].J Immunol,2017,198(12):4772-4780.
[30] Su H,Zhu S,Zhu L,et al.Recombinant lipoprotein Rv1016c derived from Mycobacterium tuberculosis is a TLR-2 ligand that induces macrophages apoptosis and inhibits MHC II antigen processing[J/OL].Front Cell Infect Microbiol,2016,6:147.DOI:10.3389/fcimb.2016.00147.
[31] Li F,Feng L,Jin C,et al.LpqT improves mycobacteria survival in macrophages by inhibiting TLR2 mediated inflammatory cytokine expression and cell apoptosis[J].Tuberculosis (Edinb),2018,111:57-66.
[32] Zhang W,Lu Q,Dong Y,et al.Rv3033,as an emerging anti-apoptosis factor,facilitates mycobacteria survival via inhibiting macrophage intrinsic apoptosis[J/OL].Front Immunol,2018,9:2136.DOI:10.3389/fimmu.2018.02136.eCollection 2018.
[33] 王士荣.抗结核药物的研究进展[J].内江科技,2018,5:82.Wang S.Progress on anti-tuberculosis drugs[J].Nei Jiang Ke Ji,2018,5:82.
[34] Sharma A,Vaghasiya K,Gupta P,et al.Reclaiming hijacked phagosomes:Hybrid nano-in-micro encapsulated MIAP peptide ensures host directed therapy by specifically augmenting phagosome-maturation and apoptosis in TB infected macrophage cells[J].Int J Pharm,2018,536(1):50-62.
[35] Amarnath Praphakar R,Jeyaraj M,Ahmed M,et al.Silver nanoparticle functionalized CS-g-(CA-MA-PZA) carrier for sustainable anti-tuberculosis drug delivery[J].Int J Biol Macromol,2018,118(Pt B):1627-1638.
[36] Machelart A,Salzano G,Li X,et al.Intrinsic antibacterial activity of nanoparticles made of β-cyclodextrins potentiates their effect as drug nanocarriers against tuberculosis[J].ACS Nano,2019,13(4):3992-4007.
[37] Su H,Zhu S,Zhu L,et al.Mycobacterium tuberculosis latent antigen Rv2029c from the multistage DNA vaccine A39 drives TH1 responses via TLR-mediated macrophage activation[J/OL].Front Microbiol,2017,8:2266.DOI:10.3389/fmicb.2017.02266.eCollection 2017.