抗弓形虫固有免疫机制研究进展

doi:10.12140/j.issn.1000-7423.2020.06.015

摘要/Abstract

摘要：

固有免疫是机体抵御病原微生物入侵的首道防线,弓形虫感染机体后能诱发有效的固有免疫应答,在限制弓形虫感染和扩散、促进适应性免疫产生等方面发挥重要作用。在固有免疫中,模式识别受体、免疫细胞、细胞因子各司其职又相互作用,构成一个复杂而有序的调节网络。细胞中的某些调节介质、转录因子调控信号转导、基因表达,广泛参与了机体的防御反应、自噬等过程。本文就宿主抗弓形虫固有免疫机制的研究进展进行综述,以期为弓形虫的防治提供科学依据。

关键词: 弓形虫感染, 固有免疫, γ干扰素

Abstract:

The innate immunity is the first defense line against invasion of pathogenic microorganisms. Toxoplasma gondii infection induces effective innate immune responses in the host, which play an important role in restricting Toxoplasma gondii infection and promoting the adaptive immunity. In the innate immunity, the pattern recognition receptors, immune cells and cytokines hold their respective roles while on the other hand interacting with each other, constituting a complex but ordered network. Some regulatory mediators and transcription factors regulate signaling transduction and gene expression, and participate in the defense response, autophagy and other biological processes. In this paper, we review the research progress of host innate immunity against T. gondii, to provide scientific basis for control of the parasite.

Key words: Toxoplasma gondii infection, Innate immunity, Interferon-γ

中图分类号:

R382.5

杜凯歌, 卓洵辉, 陆绍红. 抗弓形虫固有免疫机制研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2020, 38(6): 764-770.

DU Kai-ge, ZHUO Xun-hui, LU Shao-hong. Research advances on the innate immunity mechanisms against Toxoplasma gondii[J]. Chinese Journal of Parasitology and Parasitic Diseases, 2020, 38(6): 764-770.

参考文献 59

[1]	Saadatnia G, Golkar M. A review on human toxoplasmosis[J]. Scand J Infect Dis, 2012,44(11):805-814. doi: 10.3109/00365548.2012.693197 pmid: 22831461
[2]	Hedhli D, Moire N, Akbar H, et al. The antigen-specific response to Toxoplasma gondii profilin, a TLR11/12 ligand, depends on its intrinsic adjuvant properties[J]. Med Microbiol Immunol, 2016,205(4):345-352. doi: 10.1007/s00430-016-0452-3 pmid: 26935827
[3]	Raetz M, Kibardin A, Sturge CR, et al. Cooperation of TLR12 and TLR11 in the IRF8-dependent IL-12 response to Toxoplasma gondii profilin[J]. J Immunol, 2013,191(9):4818-4827. pmid: 24078692
[4]	Atmaca HT, Kul O, Karakus E, et al. Astrocytes, microglia/macrophages, and neurons expressing Toll-like receptor 11 contribute to innate immunity against encephalitic Toxoplasma gondii infection[J]. Neuroscience, 2014,269:184-191. doi: 10.1016/j.neuroscience.2014.03.049
[5]	Koblansky AA, Jankovic D, Oh H, et al. Recognition of profilin by Toll-like receptor 12 is critical for host resistance to Toxoplasma gondii[J]. Immunity, 2013,38(1):119-130. doi: 10.1016/j.immuni.2012.09.016
[6]	Yarovinsky F. Innate immunity to Toxoplasma gondii infection[J]. Nat Rev Immunol, 2014,14(2):109-121. doi: 10.1038/nri3598 pmid: 24457485
[7]	Tosh KW, Mittereder L, Bonne-Annee S, et al. The IL-12 response of primary human dendritic cells and monocytes to Toxoplasma gondii is stimulated by phagocytosis of live parasites rather than host cell invasion[J]. J Immunol, 2016,196(1):345-356. doi: 10.4049/jimmunol.1501558 pmid: 26597011
[8]	Mun HS, Aosai F, Norose K, et al. Toll-like receptor 4 mediates tolerance in macrophages stimulated with Toxoplasma gondii-derived heat shock protein 70[J]. Infect Immun, 2005,73(8):4634-4642. doi: 10.1128/IAI.73.8.4634-4642.2005 pmid: 16040976
[9]	Del RL, Butcher BA, Bennouna S, et al. Toxoplasma gondii triggers myeloid differentiation factor 88-dependent IL-12 and chemokine ligand 2 (monocyte chemoattractant protein 1) responses using distinct parasite molecules and host receptors[J]. J Immunol, 2004,172(11):6954-6960. doi: 10.4049/jimmunol.172.11.6954 pmid: 15153515
[10]	O’Neill LA, Golenbock D, Bowie AG. The history of Toll-like receptors-redefining innate immunity[J]. Nat Rev Immunol, 2013,13(6):453-460. doi: 10.1038/nri3446 pmid: 23681101
[11]	Costa Mendonca-Natividade F, Duque Lopes C, Ricci-Azevedo R, et al. Receptor heterodimerization and co-receptor engagement in TLR2 activation induced by MIC1 and MIC4 from Toxoplasma gondii[J]. Int J Mol Sci, 2019,20(20):5001. doi: 10.3390/ijms20205001
[12]	Diebold SS, Massacrier C, Akira S, et al. Nucleic acid agonists for Toll-like receptor 7 are defined by the presence of uridine ribonucleotides[J]. Eur J Immunol, 2006,36(12):3256-3267. doi: 10.1002/eji.200636617 pmid: 17111347
[13]	Andrade WA, Souza Mdo C, Ramos-Martinez E, et al. Combined action of nucleic acid-sensing Toll-like receptors and TLR11/TLR12 heterodimers imparts resistance to Toxoplasma gondii in mice[J]. Cell Host Microbe, 2013,13(1):42-53. doi: 10.1016/j.chom.2012.12.003
[14]	Schaiton-Kersten T, Nakajima H, Yap G, et al. Infection of mice lacking the common cytokine receptor gamma-chain (gamma(c)) reveals an unexpected role for CD4⁺ T lymphocytes in early IFN-gamma-dependent resistance to Toxoplasma gondii [J]. J Immunol, 1998,160(6):2565-2569. pmid: 9510152
[15]	Wagage S, John B, Krock BL, et al. The aryl hydrocarbon receptor promotes IL-10 production by NK cells[J]. J Immunol, 2014,192(4):1661-1670. doi: 10.4049/jimmunol.1300497 pmid: 24403534
[16]	Ivanova DL, Mundhenke TM, Gigley JP. The IL-12- and IL-23-dependent NK cell response is essential for protective immunity against secondary Toxoplasma gondii infection[J]. J Immunol, 2019,203(11):2944-2958. doi: 10.4049/jimmunol.1801525 pmid: 31604804
[17]	Schneider CA, Figueroa Velez DX, Azevedo R, et al. Imaging the dynamic recruitment of monocytes to the blood-brain barrier and specific brain regions during Toxoplasma gondii infection[J]. Proc Natl Acad Sci USA, 2019,116(49):24796-24807. doi: 10.1073/pnas.1915778116 pmid: 31727842
[18]	Biswas A, Bruder D, Wolf SA, et al. Ly6C(high) monocytes control cerebral toxoplasmosis[J]. J Immunol, 2015,194(7):3223-3235. doi: 10.4049/jimmunol.1402037 pmid: 25710908
[19]	Ehmen HG, Luder CGK. Long-term impact of Toxoplasma gondii infection on human monocytes[J]. Front Cell Infect Microbiol, 2019,9:235. doi: 10.3389/fcimb.2019.00235 pmid: 31316920
[20]	Safronova A, Araujo A, Camanzo ET, et al. Alarmin S100A11 initiates a chemokine response to the human pathogen Toxoplasma gondii[J]. Nat Immunol, 2019,20(1):64-72. doi: 10.1038/s41590-018-0250-8 pmid: 30455460
[21]	Arsenijevic D, Bilbao FD, Giannakopoulos P, et al. A role for interferon-gamma in the hypermetabolic response to murine toxoplasmosis[J]. Eur Cytokine Netw, 2001,12(3):518-527. pmid: 11566633
[22]	Sturge CR, Benson A, Raetz M, et al. TLR-independent neutrophil-derived IFN-gamma is important for host resistance to intracellular pathogens[J]. Proc Natl Acad Sci USA, 2013,110(26):10711-10716. doi: 10.1073/pnas.1307868110 pmid: 23754402
[23]	Sturge CR, Yarovinsky F. Complex immune cell interplay in the gamma interferon response during Toxoplasma gondii infection[J]. Infect Immun, 2014,82(8):3090-3097. doi: 10.1128/IAI.01722-14
[24]	Qu Y, Wang S, Fan ZS. Research progress on the biological functions and immunoregulatory effects of innate lymphoid cells[J]. Prog Biochem Biophys, 2018,45(9):897-914. (in Chinese)
	( 渠源, 王硕, 范祖森. ILC细胞的生物学功能与免疫调节作用[J]. 生物化学与生物物理进展, 2018,45(9):897-914.)
[25]	Zhang C, Tian ZG. Innate lymphoid cells and inflammatory diseases[J]. Cell Mol Immunol, 2019,35(6):641-647. (in Chinese)
	( 张彩, 田志刚. ILC细胞与自身炎症性疾病[J]. 中国免疫学杂志, 2019,35(6):641-647.)
[26]	Ivanova DL, Denton SL, Fettel KD, et al. Innate lymphoid cells in protection, pathology, and adaptive immunity during apicomplexan infection[J]. Front Immunol, 2019,10:196. doi: 10.3389/fimmu.2019.00196 pmid: 30873151
[27]	Shah S, Grotenbreg GM, Rivera A, et al. An extrafollicular pathway for the generation of effector CD8(+) T cells driven by the proinflammatory cytokine, IL-12[J]. eLife, 2015,4:e09017. doi: 10.7554/eLife.09017
[28]	Suzuki Y. The immune system utilizes two distinct effector mechanisms of T cells depending on two different life cycle stages of a single pathogen, Toxoplasma gondii, to control its cerebral infection[J]. Parasitol Int, 2020,76:102030. doi: 10.1016/j.parint.2019.102030 pmid: 31778800
[29]	Ufermann CM, Domrose A, Babel T, et al. Indoleamine 2,3-dioxygenase activity during acute toxoplasmosis and the suppressed T cell proliferation in mice[J]. Front Cell Infect Microbiol, 2019,9:184. doi: 10.3389/fcimb.2019.00184 pmid: 31231617
[30]	Yeung AW, Terentis AC, King NJ, et al. Role of indoleamine 2,3-dioxygenase in health and disease[J]. Clin Sci (Lond), 2015,129(7):601-672. doi: 10.1042/CS20140392
[31]	Muller UB, Howard JC. The impact of Toxoplasma gondii on the mammalian genome[J]. Curr Opin Microbiol, 2016,32:19-25. doi: 10.1016/j.mib.2016.04.009 pmid: 27128504
[32]	Meunier E, Broz P. Interferon-inducible GTPases in cell autonomous and innate immunity[J]. Cell Microbiol, 2016,18(2):168-180. doi: 10.1111/cmi.12546 pmid: 26572694
[33]	Lee Y, Yamada H, Pradipta A, et al. Initial phospholipid-dependent Irgb6 targeting to Toxoplasma gondii vacuoles mediates host defense[J]. Life Sci Alliance, 2019,3(1):e201900549. doi: 10.26508/lsa.201900549 pmid: 31852733
[34]	Bekpen C, Hunn JP, Rohde C, et al. The interferon-inducible p47 (IRG) GTPases in vertebrates: loss of the cell autonomous resistance mechanism in the human lineage[J]. Genome Biol, 2005,6(11):R92. doi: 10.1186/gb-2005-6-11-r92 pmid: 16277747
[35]	Saeij JP, Frickel EM. Exposing Toxoplasma gondii hiding inside the vacuole: a role for GBPs, autophagy and host cell death[J]. Curr Opin Microbiol, 2017,40:72-80. doi: 10.1016/j.mib.2017.10.021 pmid: 29141239
[36]	Degrandi D, Kravets E, Konermann C, et al. Murine guanylate binding protein 2 (mGBP2) controls Toxoplasma gondii replication[J]. Proc Natl Acad Sci USA, 2013,110(1):294-299. doi: 10.1073/pnas.1205635110 pmid: 23248289
[37]	Selleck EM, Fentress SJ, Beatty WL, et al. Guanylate-binding protein 1 (Gbp1) contributes to cell-autonomous immunity against Toxoplasma gondii[J]. PLoS Pathog, 2013,9(4):e1003320. doi: 10.1371/journal.ppat.1003320 pmid: 23633952
[38]	Yamamoto M, Okuyama M, Ma JS, et al. A cluster of interferon-gamma-inducible p65 GTPases plays a critical role in host defense against Toxoplasma gondii[J]. Immunity, 2012,37(2):302-313. doi: 10.1016/j.immuni.2012.06.009 pmid: 22795875
[39]	Selleck EM, Orchard RC, Lassen KG, et al. A noncanonical autophagy pathway restricts Toxoplasma gondii growth in a strain-specific manner in IFN-gamma-activated human cells[J]. mBio, 2015,6(5):e01157-15. doi: 10.1128/mBio.01157-15 pmid: 26350966
[40]	Ohshima J, Lee Y, Sasai M, et al. Role of mouse and human autophagy proteins in IFN-γ-induced cell-autonomous responses against Toxoplasma gondii[J]. J Immunol, 2014,192(7):3328-3335. doi: 10.4049/jimmunol.1302822 pmid: 24563254
[41]	Johnston AC, Piro A, Clough B, et al. Human GBP1 does not localize to pathogen vacuoles but restricts Toxoplasma gondii[J]. Cell Microbiol, 2016,18(8):1056-1064. doi: 10.1111/cmi.12579 pmid: 26874079
[42]	Qin A, Lai DH, Liu Q, et al. Guanylate-binding protein 1 (GBP1) contributes to the immunity of human mesenchymal stromal cells against Toxoplasma gondii[J]. Proc Natl Acad Sci USA, 2017,114(6):1365-1370. pmid: 28123064
[43]	Fox BA, Gigley JP, Bzik DJ. Toxoplasma gondii lacks the enzymes required for de novo arginine biosynjournal and arginine starvation triggers cyst formation[J]. Int J Parasitol, 2004,34(3):323-331. doi: 10.1016/j.ijpara.2003.12.001 pmid: 15003493
[44]	Sa Q, Tiwari A, Ochiai E, et al. Inducible nitric oxide synthase in innate immune cells is important for restricting cyst formation of Toxoplasma gondii in the brain but not required for the protective immune process to remove the cysts[J]. Microbes Infect, 2018,20(4):261-266. doi: 10.1016/j.micinf.2017.12.004 pmid: 29287983
[45]	Bando H, Lee Y, Sakaguchi N, et al. Inducible nitric oxide synthase is a key host factor for Toxoplasma GRA15-dependent disruption of the gamma interferon-induced antiparasitic human response[J]. mBio, 2018,9(5):e01738-18. doi: 10.1128/mBio.01738-18 pmid: 30301855
[46]	Cohen SB, Smith NL, McDougal C, et al. Beta-catenin signaling drives differentiation and proinflammatory function of IRF8-dependent dendritic cells[J]. J Immunol, 2015,194(1):210-222. pmid: 25416805
[47]	Nast R, Staab J, Meyer T, et al. Toxoplasma gondii stabilises tetrameric complexes of tyrosine-phosphorylated signal transducer and activator of transcription-1 and leads to its sustained and promiscuous DNA binding[J]. Cell Microbiol, 2018,20(11):e12887. doi: 10.1111/cmi.12887 pmid: 29968354
[48]	Gay G, Braun L, Brenier-Pinchart MP, et al. Toxoplasma gondii TgIST coopts host chromatin repressors dampening STAT1-dependent gene regulation and IFN-γ-mediated host defenses[J]. J Exp Med, 2016,213(9):1779-1798. doi: 10.1084/jem.20160340 pmid: 27503074
[49]	Mammari N, Halabi MA, Yaacoub S, et al. Toxoplasma gondii modulates the host cell responses: an overview of apoptosis pathways[J]. Biomed Res Int, 2019,2019:6152489. pmid: 31080827
[50]	Braun L, Brenier-Pinchart MP, Hammoudi PM, et al. The Toxoplasma effector TEEGR promotes parasite persistence by modulating NF-κB signalling via EZH2[J]. Nat Microbiol, 2019,4(7):1208-1220. doi: 10.1038/s41564-019-0431-8 pmid: 31036909
[51]	Jin Y, Yao Y, El-Ashram S, et al. The neurotropic parasite Toxoplasma gondii induces astrocyte polarization through NFκB pathway[J]. Front Med (Lausanne), 2019,6:267.
[52]	Besteiro S. The role of host autophagy machinery in controlling Toxoplasma infection[J]. Virulence, 2019,10(1):438-447. doi: 10.1080/21505594.2018.1518102 pmid: 30269643
[53]	Choi JW, Lee J, Lee JH, et al. Omega-3 polyunsaturated fatty acids prevent Toxoplasma gondii infection by inducing autophagy via AMPK activation[J]. Nutrients, 2019,11(9):2137.
[54]	Haldar AK, Piro AS, Pilla DM, et al. The E2-like conjugation enzyme Atg3 promotes binding of IRG and Gbp proteins to Chlamydia- and Toxoplasma-containing vacuoles and host resistance[J]. PLoS One, 2014,9(1):e86684. doi: 10.1371/journal.pone.0086684 pmid: 24466199
[55]	Zhao Z, Fux B, Goodwin M, et al. Autophagosome-independent essential function for the autophagy protein Atg5 in cellular immunity to intracellular pathogens[J]. Cell Host Microbe, 2008,4(5):458-469. doi: 10.1016/j.chom.2008.10.003 pmid: 18996346
[56]	Liu E, Lopez Corcino Y, Portillo JA, et al. Identification of signaling pathways by which CD40 stimulates autophagy and antimicrobial activity against Toxoplasma gondii in macrophages[J]. Infect Immun, 2016,84(9):2616-2626. doi: 10.1128/IAI.00101-16 pmid: 27354443
[57]	Choi J, Biering SB, Hwang S. Quo vadis interferon-inducible GTPases go to their target membranes via the LC3-conjugation system of autophagy[J]. Small GTPases, 2017,8(4):199-207. doi: 10.1080/21541248.2016.1213090 pmid: 27428166
[58]	Subauste CS. Interplay between Toxoplasma gondii, autophagy, and autophagy proteins[J]. Front Cell Infect Microbiol, 2019,9:139. doi: 10.3389/fcimb.2019.00139 pmid: 31119109
[59]	Bando H, Sakaguchi N, Lee Y, et al. Toxoplasma effector TgIST targets host IDO1 to antagonize the IFN-γ-induced anti-parasitic response in human cells[J]. Front Immunol, 2018,9:2073. doi: 10.3389/fimmu.2018.02073 pmid: 30283439