巨噬细胞表型在鼠疫杆菌和牛布鲁氏杆菌联合免疫效果早期评价中的潜在作用
|
摘要
目的在需要多种疫苗同时免疫的应急情况下,如何快速评价联合免疫的效果是目前迫切需要解决的问题。本研究旨在探究巨噬细胞表型变化在早期快速评价鼠疫杆菌和布氏杆菌联合免疫效果中的潜在作用及其可能的应用价值。方法建立鼠疫杆菌、牛布鲁氏杆菌疫苗小鼠免疫模型,分别在免疫早期(4 d)和免疫后期(14 d)检测巨噬细胞表型(M1或M2极化)差异,及CD8+T细胞表型功能的变化,分析早期巨噬细胞免疫表型对后期CD8+T细胞功能的影响。结果在联合免疫早期,鼠疫杆菌及牛布鲁氏杆菌同时免疫情况下巨噬细胞M1方向的极化减弱(包括细胞表面CD16/32表达降低及Detectin-1表达升高,细胞内IL-12表达降低及IL-4表达升高),提示疫苗间的相互干扰。同时,两菌联合接种组CD8+T细胞的活性(包括CD8+CD69+T、CD8+INF-γ+T以及CD8+Granzyme B+T细胞的比例)也减弱,出现与巨噬细胞表型一致的变化趋势。结论联合免疫早期巨噬细胞表型与后期反映抗感染免疫应答能力的CD8+T细胞表型及功能出现一致性变化,提示巨噬细胞表型变化有可能应用于早期快速评价联合免疫的效果。
Objective In emergency situations where simultaneous immunization by multiple vaccines are required, how to rapidly evaluate the effect of combined immunization is an urgent issue that needs to be solved. This study aimed to investigate the potential role and application value of the phenotypic changes of macrophages in rapid evaluation of the effect of combined Yersinia pestis and Brucella bovis vaccine immunization at early stage. Methods Y. pestis and B. bovis vaccines were injected into mice alone or in combination to establish animal models. The changes of the macrophage phenotypes(M1 or M2 polarization)and the CD8+T cell phenotypes and functions were detected in the early(4 d)and the late(14 d)stage of the immunization,respectively. The effect of the immunophenotype of macrophages at early stage on the function of CD8+T cells at late stage was analyzed. Results The co-immunization by Y. pestis and B. bovis vaccines led to the attenuation of the M1-polarization of macrophages at early stage,which were marked by decreased expression of CD16/32 and increased expression of Detectin-1 on cell surface as well as decreased expression of IL-12 and increased expression of IL-4 inside the macrophage, in comparison with single vaccine groups, suggesting an interference between the two vaccines. Meanwhile,the activity of CD8+T cells(including the ratio of CD8+CD69+T,CD8+IFN-γ+T and CD8+Granzyme B+T cells)in combined immunization group showed similar tendency to the attenuated phenotypic M1-polarization of macrophages. Conclusion The phenotype of macrophages at the early stage of the co-immunization by Y. pestis and B. bovis vaccines showed consistency with the phenotype and function of CD8+T cells at late stage. It might give us some hint about the possibility of utilizing the phenotypic changes of macrophages to rapidly evaluate the effect of the co-immunization at early stage.
Objective In emergency situations where simultaneous immunization by multiple vaccines are required, how to rapidly evaluate the effect of combined immunization is an urgent issue that needs to be solved. This study aimed to investigate the potential role and application value of the phenotypic changes of macrophages in rapid evaluation of the effect of combined Yersinia pestis and Brucella bovis vaccine immunization at early stage. Methods Y. pestis and B. bovis vaccines were injected into mice alone or in combination to establish animal models. The changes of the macrophage phenotypes(M1 or M2 polarization)and the CD8+T cell phenotypes and functions were detected in the early(4 d)and the late(14 d)stage of the immunization,respectively. The effect of the immunophenotype of macrophages at early stage on the function of CD8+T cells at late stage was analyzed. Results The co-immunization by Y. pestis and B. bovis vaccines led to the attenuation of the M1-polarization of macrophages at early stage,which were marked by decreased expression of CD16/32 and increased expression of Detectin-1 on cell surface as well as decreased expression of IL-12 and increased expression of IL-4 inside the macrophage, in comparison with single vaccine groups, suggesting an interference between the two vaccines. Meanwhile,the activity of CD8+T cells(including the ratio of CD8+CD69+T,CD8+IFN-γ+T and CD8+Granzyme B+T cells)in combined immunization group showed similar tendency to the attenuated phenotypic M1-polarization of macrophages. Conclusion The phenotype of macrophages at the early stage of the co-immunization by Y. pestis and B. bovis vaccines showed consistency with the phenotype and function of CD8+T cells at late stage. It might give us some hint about the possibility of utilizing the phenotypic changes of macrophages to rapidly evaluate the effect of the co-immunization at early stage.
引文
[1]Watanabe M,Nishikomori R,Fujimaki Y,et al.Live-attenuated vaccines in a cryopyrin-associated periodic syndrome patient receiving canakinumab treatment during infancy[J].Clin Case Rep,2017,5(11):1750-1755.
[2]Vasudevan A,Woerner A,Schmeisser F,et al.Potency determination of inactivated H7 influenza vaccines using monoclonal antibody-based ELISA and biolayer interferometry assays[J].Influenza Other Respir Viruses,2017,12(2):250-258.
[3]Rojas JM,Avia M,Pascual E,et al.Vaccination with recombinant adenovirus expressing peste des petitsruminants virus-F orH proteins elicits T cell responses to epitopes that arises during PPRV infection[J].Vet Res,2017,48(1):79.
[4]Sobhkhez M,Krasnov A,Chang CJ,et al.Transcriptome analysis of plasmid-induced genes sheds light on the role of type I IFN as adjuvant in DNA vaccine against infectious salmon anemia virus[J].PLo S One,2017,12(11):e0188456.
[5]侯启明,马宵,张庶民.百白破联合疫苗基础免疫后不同时间的抗体水平研究[J].中国计划免疫,2004,2:81-83.
[6]Ebbo M,Crinier A,Vély F,et al.Innate lymphoid cells:major players in inflammatory diseases[J].Nat Rev Immunol,2017,17(11):665-678.
[7]Bollard CM,Heslop HE.T cells for viral infections after allogeneic hematopoietic stem cell transplant[J].Blood,2016,127(26):3331-3340.
[8]Arora S,Dev K,Agarwal B,et al.Macrophages:Their role,activation and polarization in pulmonary diseases[J].Immunobiology,2018,223(4/5):383-396.
[9]Bou Nasser Eddine F,Ramia E,et al.Tumor immunology meets…immunology:modified cancer cells as professional APC for priming na?ve tumor-specific CD4+T cells[J].Oncoimmunology,2017,6(11):e1356149.
[10]Johnson RMG,Dong H.Functional expression of programmed death-ligand 1(B7-H1)by immune cells and tumor cells[J].Front Immunol,2017,8:961-968.
[11]Kumar R,Chauhan SB,Ng SS,et al.Immune checkpoint targets for host-directed therapy to prevent and treat Leishmaniasis[J].Front Immunol,2017,8:1492-1505.
[12]Fan D,Li W,Yang Y,et al.Redirection of CD4+and CD8+T lymphocytes via an anti-CD3×anti-CD19 bi-specific antibody combined with cytosine arabinoside and the efficient lysis of patient-derived B-ALL cells[J].J Hematol Oncol,2015,8:108-119.
[13]Bose A,Chakraborty T,Chakraborty K,et al.Dysregulation in immune functions is reflected in tumor cell cytotoxicity by peripheral blood mononuclear cells from head and neck squamous cell carcinoma patients[J].Cancer Immun,2008,8:10.
[14]Zaric M,Becker PD,Hervouet C,et al.Long-lived tissue resident HIV-1 specific memory CD8+T cells are generated by skin immunization with live virus vectored microneedle arrays[J].J Control Release,2017,268:166-175.
[15]Fisker AB,Nebie E4,Schoeps A,et al.A two-centrerandomised trial of an additional early dose of measles vaccine:effects on mortality and measles antibody levels[J].Clin Infect Dis,2017,12:cix1033.
[2]Vasudevan A,Woerner A,Schmeisser F,et al.Potency determination of inactivated H7 influenza vaccines using monoclonal antibody-based ELISA and biolayer interferometry assays[J].Influenza Other Respir Viruses,2017,12(2):250-258.
[3]Rojas JM,Avia M,Pascual E,et al.Vaccination with recombinant adenovirus expressing peste des petitsruminants virus-F orH proteins elicits T cell responses to epitopes that arises during PPRV infection[J].Vet Res,2017,48(1):79.
[4]Sobhkhez M,Krasnov A,Chang CJ,et al.Transcriptome analysis of plasmid-induced genes sheds light on the role of type I IFN as adjuvant in DNA vaccine against infectious salmon anemia virus[J].PLo S One,2017,12(11):e0188456.
[5]侯启明,马宵,张庶民.百白破联合疫苗基础免疫后不同时间的抗体水平研究[J].中国计划免疫,2004,2:81-83.
[6]Ebbo M,Crinier A,Vély F,et al.Innate lymphoid cells:major players in inflammatory diseases[J].Nat Rev Immunol,2017,17(11):665-678.
[7]Bollard CM,Heslop HE.T cells for viral infections after allogeneic hematopoietic stem cell transplant[J].Blood,2016,127(26):3331-3340.
[8]Arora S,Dev K,Agarwal B,et al.Macrophages:Their role,activation and polarization in pulmonary diseases[J].Immunobiology,2018,223(4/5):383-396.
[9]Bou Nasser Eddine F,Ramia E,et al.Tumor immunology meets…immunology:modified cancer cells as professional APC for priming na?ve tumor-specific CD4+T cells[J].Oncoimmunology,2017,6(11):e1356149.
[10]Johnson RMG,Dong H.Functional expression of programmed death-ligand 1(B7-H1)by immune cells and tumor cells[J].Front Immunol,2017,8:961-968.
[11]Kumar R,Chauhan SB,Ng SS,et al.Immune checkpoint targets for host-directed therapy to prevent and treat Leishmaniasis[J].Front Immunol,2017,8:1492-1505.
[12]Fan D,Li W,Yang Y,et al.Redirection of CD4+and CD8+T lymphocytes via an anti-CD3×anti-CD19 bi-specific antibody combined with cytosine arabinoside and the efficient lysis of patient-derived B-ALL cells[J].J Hematol Oncol,2015,8:108-119.
[13]Bose A,Chakraborty T,Chakraborty K,et al.Dysregulation in immune functions is reflected in tumor cell cytotoxicity by peripheral blood mononuclear cells from head and neck squamous cell carcinoma patients[J].Cancer Immun,2008,8:10.
[14]Zaric M,Becker PD,Hervouet C,et al.Long-lived tissue resident HIV-1 specific memory CD8+T cells are generated by skin immunization with live virus vectored microneedle arrays[J].J Control Release,2017,268:166-175.
[15]Fisker AB,Nebie E4,Schoeps A,et al.A two-centrerandomised trial of an additional early dose of measles vaccine:effects on mortality and measles antibody levels[J].Clin Infect Dis,2017,12:cix1033.