Role of toll-like receptor 4 in eliciting adaptive immune responses against recombinant BCG expressing the C-terminus of merozoite surface protein-1 of Plasmodium falciparum
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摘要
Objective: To determine the role of toll-like receptor 4(TLR-4) in eliciting cellular and humoral immune responses against recombinant Mycobacterium bovis bacille Calmette-Guérin(rB CG) expressing the C-terminus of merozoite surface protein-1 of Plasmodium falciparum. Methods: Six groups of mice(n=6 per group) were injected with phosphate buffered saline T80, BCG or r BCG intraperitoneally, in the presence or absence of a TLR-4 inhibitor; TAK-242. Enzyme-linked immunosorbent assay was carried out for serum total IgG, IgG 1, Ig G2 a and Ig G2 b determination. Spleens were also harvested and splenocytes cultured for determination of intracellular cytokines; IL-4 and IFN-毭 via enzyme-linked immunosorbent assay. Results: The production of total Ig G, and the subclasses Ig G1, Ig G2 a and Ig G2 b was significantly higher in rB CG-immunised mice than BCG and phosphate buffered saline immunised mice in the absence of TAK-242. A significant rise in total IgG occurred with more booster immunisations. The level of IgG 2 a was highest, followed by IgG 2 b, then IgG 1. The production of both IL-4 and IFN-were inhibited in t毭 was also highest in the rB CG immunised groups. These significant riseshe presence of TAK-242. Conclusions: We present evidence of the role of TLR-4 in the increased production of total IgG, IgG 1, IgG 2 a and IgG 2 b, as well as IL-4 and IFN-毭 in response to our rB CG construct.
Objective: To determine the role of toll-like receptor 4(TLR-4) in eliciting cellular and humoral immune responses against recombinant Mycobacterium bovis bacille Calmette-Guérin(rB CG) expressing the C-terminus of merozoite surface protein-1 of Plasmodium falciparum. Methods: Six groups of mice(n=6 per group) were injected with phosphate buffered saline T80, BCG or r BCG intraperitoneally, in the presence or absence of a TLR-4 inhibitor; TAK-242. Enzyme-linked immunosorbent assay was carried out for serum total IgG, IgG 1, Ig G2 a and Ig G2 b determination. Spleens were also harvested and splenocytes cultured for determination of intracellular cytokines; IL-4 and IFN-毭 via enzyme-linked immunosorbent assay. Results: The production of total Ig G, and the subclasses Ig G1, Ig G2 a and Ig G2 b was significantly higher in rB CG-immunised mice than BCG and phosphate buffered saline immunised mice in the absence of TAK-242. A significant rise in total IgG occurred with more booster immunisations. The level of IgG 2 a was highest, followed by IgG 2 b, then IgG 1. The production of both IL-4 and IFN-were inhibited in t毭 was also highest in the rB CG immunised groups. These significant riseshe presence of TAK-242. Conclusions: We present evidence of the role of TLR-4 in the increased production of total IgG, IgG 1, IgG 2 a and IgG 2 b, as well as IL-4 and IFN-毭 in response to our rB CG construct.
Objective: To determine the role of toll-like receptor 4(TLR-4) in eliciting cellular and humoral immune responses against recombinant Mycobacterium bovis bacille Calmette-Guérin(rB CG) expressing the C-terminus of merozoite surface protein-1 of Plasmodium falciparum. Methods: Six groups of mice(n=6 per group) were injected with phosphate buffered saline T80, BCG or r BCG intraperitoneally, in the presence or absence of a TLR-4 inhibitor; TAK-242. Enzyme-linked immunosorbent assay was carried out for serum total IgG, IgG 1, Ig G2 a and Ig G2 b determination. Spleens were also harvested and splenocytes cultured for determination of intracellular cytokines; IL-4 and IFN-毭 via enzyme-linked immunosorbent assay. Results: The production of total Ig G, and the subclasses Ig G1, Ig G2 a and Ig G2 b was significantly higher in rB CG-immunised mice than BCG and phosphate buffered saline immunised mice in the absence of TAK-242. A significant rise in total IgG occurred with more booster immunisations. The level of IgG 2 a was highest, followed by IgG 2 b, then IgG 1. The production of both IL-4 and IFN-were inhibited in t毭 was also highest in the rB CG immunised groups. These significant riseshe presence of TAK-242. Conclusions: We present evidence of the role of TLR-4 in the increased production of total IgG, IgG 1, IgG 2 a and IgG 2 b, as well as IL-4 and IFN-毭 in response to our rB CG construct.
引文
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[2]Arévalo-Herrera M,Rengifo L,Lopez-Perez M,Arce-Plata MI,García J,Herrera S.Complicated malaria in children and adults from three settings of the Colombian Pacific Coast:A prospective study.Plo S One 2017;12(9):e0185435.Doi:10.1371/journal.pone.0185435.
[3]Batool SM.Malaria in pregnant women.Int J Infect 2015;2(3):e22992.
[4]Blasco B,Leroy D,Fidock DA.Antimalarial drug resistance:Linking Plasmodium falciparum parasite biology to the clinic.Nat Med 2017;23(8):917-928.
[5]Aung MT,Aung PP,Jordi L,Daniel MP,Francois HN.Combating multidrug-resistant Plasmodium falciparum malaria.FEBS J 2017;284:2569-2578.
[6]Hanson MS,Bansal GP,Langermann S,Stover CK,Orme I.Efficacy and safety of live recombinant BCG vaccines.Dev Biol Stand 1995;84:229-236.
[7]Stover CK,de la Cruz VF,Fuerst TR,Burlein JE,Benson LA,Bennett LT,et al.New use of BCG for recombinant vaccines.Nature 1991;351:456.
[8]Mandavi K,Rajiv KS.Relative efficacy of uptake and presentation of Mycobacterium bovis BCG antigens by type栺mouse lung epithelial cells and peritoneal macrophages.Infect Immun 2011;79(8):3159-3167.
[9]Djuardi Y,Sartono E,Wibowo H,Supali T,Yazdanbakhsh M.Alongitudinal study of BCG vaccination in early childhood:The development of innate and adaptive immune responses.PLo S One 2010;5(11):e14066.
[10]Yu X,Prados-Rosales R,Jenny-Avital ER,Sosa K,Casadevall A,Achkar JM.Comparative evaluation of profiles of antibodies to mycobacterial capsular polysaccharides in tuberculosis patients and controls stratified by HIV status.Clin Vaccine Immunol 2012;19(2):198-208.
[11]Kleinnijenhuis J,Quintin J,Preijers F,Joosten LA,Ifrim DC,Saeed S,et al.Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes.Proc Natl Acad Sci U S A 2012;109(43):17537-17542.
[12]Fowkes FJ,Richards JS,Simpson JA,Beeson JG.The relationship between anti-merozoite antibodies and incidence of Plasmodium falciparum malaria:A systematic review and meta-analysis.PLo S Med2010;7(1):e1000218.
[13]O’Donnell RA,de Koning-Ward TF,Burt RA,Bockarie M,Reeder JC,Cowman AF,et al.Antibodies against merozoite surface protein(MSP)-1(19)are a major component of the invasion inhibitory response in individuals immune to malaria.J Exp Med 2001;193(12):1403-1412.
[14]Bisseye C,Yindom LM,SimporéJ,Morgan WD,Holder AA,Ismaili J.An engineered Plasmodium falciparum C-terminal 19-kilodalton merozoite surface protein 1 vaccine candidate induces high levels of interferon-gamma production associated with cellular immune responses to specific peptide sequences in Gambian adults naturally exposed to malaria.Clin Exp Immunol 2011;166(3):366-373.
[15]Dodoo D,Aikins A,Kusi KA,Lamptey H,Remarque E,Milligan P,et al.Cohort study of the association of antibody levels to AMA1 MSP119MSP3 and GLURP with protection from clinical malaria in Ghanaian children.Malar J 2008;7:142.
[16]Hirunpetcharat C,Tian JH,Kaslow DC,van Rooijen N,Kumar S,Berzofsky JA,et al.Complete protective immunity induced in mice by immunization with the 19-kilodalton carboxyl-terminal fragment of the merozoite surface protein-1(MSP1[19])of Plasmodium yoelii expressed in Saccharomyces cerevisiae:Correlation of protection with antigenspecific antibody titer but not with effector CD4z T cells.J Immunol1997;159(7):3400-3411.
[17]Nurul AA,Norazmi MN.Immunogenicity and in vitro protective efficacy of recombinant Mycobacterium bovis bacille Calmette Guerin(r BCG)expressing the 19 k Da merozoite surface protein-1(MSP-1(19))antigen of Plasmodium falciparum.Parasitol Res 2011;108(4):887-897.
[18]Goel VK,Li X,Chen H,Liu SC,Chishti AH,Oh SS.Band 3 is a host receptor binding merozoite surface protein 1 during the Plasmodium falciparum invasion of erythrocytes.Proc Natl Acad Sci U S A 2003;100(9):5164-5169.
[19]Saiga H,Shimada Y,Takeda K.Innate immune effectors in mycobacterial infection.Clin Dev Immunol 2011;2011:347594.
[20]Cui J,Chen Y,Wang HY,Wang RF.Mechanisms and pathways of innate immune activation and regulation in health and cancer.Hum Vaccin Immunother 2014;10(11):3270-3285.
[21]Medzhitov R.Recognition of microorganisms and activation of the immune response.Nature 2007;449(7164):819-826.
[22]Barboza R,Lima FA,Reis,AS,Murillo OJ,Peixoto E,Bandeira CL,et al.TLR4-mediated placental pathology and pregnancy outcome in experimental malaria.Sci Rep 2017;7(1):8623.Doi:10.1038/s41598-017-08299-x.
[23]Gun SY,Claser C,Tan KS,Renia L.Interferons and interferon regulatory factors in malaria.Mediators Inflamm 2014;2014:243713.
[24]Rosadini CV,Kagan JC.Early innate immune responses to bacterial LPS.Curr Opin Immunol 2017;44:14-19.
[25]Ailian Z,Yu Y,Yan W,Gan Z,Xiumei Y,Danyang W,et al.Adjuvantactive aqueous extracts from Artemisia rupestris L.improve immune responses through TLR4 signaling pathway.Vaccine 2017;35:1037-1045.
[26]Collins AM.Ig G subclass co-expression brings harmony to the quartet model of murine Ig G function.Immunol Cell Biol 2016;94(10):949-954.Doi:10.1038/icb.2016.65.
[27]Fatin M,Nawwab A,Sue DX,Charles M,Kirsty W,Ross LC,et al.Magnetic nanovectors for the development of DNA blood‐stage malaria vaccines.Nanomaterials 2017;7(2):30.Doi:10.3390/nano7020030.
[28]Gustavo CM,Matthew DH,Mona OM,Ariane CG,Paul E,Amy F,et al.Virus-like particle(VLP)plus microcrystalline tyrosine(MCT)adjuvants enhance vaccine efficacy improving T and B cell immunogenicity and protection against Plasmodium berghei/vivax.Vaccines 2017;5(2):10.Doi:10.3390/vaccines5020010.
[29]Cherif MK,Ouédraogo O,Sanou GS,Diarra A,Ouédraogo A,Tiono A,et al.Antibody responses to P.falciparum blood stage antigens and incidence of clinical malaria in children living in endemic area in Burkina Faso.BMC Research Notes 2017;10(1):472.Doi:10.1186/s13104-017-2772-9.
[30]Natharinee H,Kiattawee C,Siriluk R,Jarinee T,Srisin K.Acquisition of naturally acquired antibody response to Plasmodium falciparum erythrocyte membrane protein 1-DBLa and differential regulation of Ig Gsubclasses in severe and uncomplicated malaria.Asian Pac J Trop Biomed2017;7(12):1055-1061.
[31]Reyes-Sandoval A,Wyllie DH,Bauza K,Milicic A,Forbes EK,Rollier CS,et al.CD8+T effector memory cells protect against liver-stage malaria.J Immunol 2011;187(3):1347-1357.
[32]Anchang-Kimbi JK,Achidi EA,Nkegoum B,Mendimi JMN,Sverremark-Ekstr?m E,Troye-Blomberg M.Ig G isotypic antibodies to crude Plasmodium falciparum blood-stage antigen associated with placental malaria infection in parturient Cameroonian women.Afri Health Sci 2016;16(4):1007-1017.Doi:10.4314/ahs.v16i4.17.
[33]Weaver R,Reiling L,Feng G,Drew DR,Mueller I,Siba PM,et al.The association between naturally acquired Ig G subclass specific antibodies to the Pf RH5 invasion complex and protection from Plasmodium falciparum malaria.Sci Rep 2016;6:33094.Doi:10.1038/srep33094.
[34]Saavedra-Langer R,Marapara J,Valle-Campos A,Durand S,VásquezChasnamote ME,Silva,H,et al.Ig G subclass responses to excretedsecreted antigens of Plasmodium falciparum in a low-transmission malaria area of the Peruvian Amazon.Malar J 2018;17(1):328.Doi:10.1186/s12936-018-2471-6.
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