Research advances on host cell-autonomous immunity against Toxoplasma gondii

doi:10.12140/j.issn.1000-7423.2024.05.014

Abstract

Abstract:

Toxoplasma gondii is one of the most common infectious agents in humans and animals, causing zoonotic toxoplasmosis, which poses a serious hazard to human health and animal husbandry production. Cell-autonomous immunity is an intrinsic immune response that occurs within individual cells to limit the replication and spread of pathogens (e.g., bacteria, viruses, parasites, etc.) that invade the cells. After infection of host cells by T. gondii, cell-autonomous immunity is mainly regulated by interferon-induced indoleamine 2,3-dioxygenase (IDO), inducible nitric oxide synthase (iNOS), GTPase family enzymes, autophagy-related proteins, and ubiquitylation products, all of which play an important role in host cell resistance to T. gondii. In this paper, we reviewed the research advances on the autonomous immune response of host cell against T. gondii, aiming to provide new directions for the prevention and treatment of toxoplasmosis.

Key words: Toxoplasma gondii, Cell-autonomous immunity, Interferon-γ

CLC Number:

R382.5

LI Shiyu, LI Jing, LU Shaohong, ZHENG Bin. Research advances on host cell-autonomous immunity against Toxoplasma gondii[J]. CHINESE JOURNAL OF PARASITOLOGY AND PARASITIC DISEASES, 2024, 42(5): 653-658.

Figures/Tables 1

References 74

[1]	Zhao XY, Ewald SE. The molecular biology and immune control of chronic Toxoplasma gondii infection[J]. J Clin Invest, 2020, 130(7): 3370-3380.
[2]	Loh FK, Nathan S, Chow SC, et al. Vaccination challenges and strategies against long-lived Toxoplasma gondii[J]. Vaccine, 2019, 37(30): 3989-4000.
[3]	Wei F, Wang W, Liu Q. Protein kinases of Toxoplasma gondii: functions and drug targets[J]. Parasitol Res, 2013, 112(6): 2121-2129.
[4]	Costa Mendonça-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.
[5]	Nyonda MA, Hammoudi PM, Ye S, et al. Toxoplasma gondii GRA60 is an effector protein that modulates host cell autonomous immunity and contributes to virulence[J]. Cell Microbiol, 2021, 23(2): e13278.
[6]	Rastogi S, Xue Y, Quake SR, et al. Differential impacts on host transcription by ROP and GRA effectors from the intracellular parasite Toxoplasma gondii[J]. mBio, 2020, 11(3): e00182.
[7]	Sasai M, Yamamoto M. Innate, adaptive, and cell-autonomous immunity against Toxoplasma gondii infection[J]. Exp Mol Med, 2019, 51(12): 1-10. doi: 10.1038/s12276-019-0353-9 pmid: 31827072
[8]	Ihara F, Yamamoto M. The role of IFN-γ-mediated host immune responses in monitoring and the elimination of Toxoplasma gondii infection[J]. Int Immunol, 2024, 36(5): 199-210.
[9]	Du KG, Zhuo XH, Lu SH. Research advances on the innate immunity mechanisms against Toxoplasma gondii[J]. Chin J Parasitol Parasit Dis, 2020, 38(6): 764-770. (in Chinese)
	(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.) doi: 10.12140/j.issn.1000-7423.2020.06.015
[10]	Bonilla FA, Oettgen HC. Adaptive immunity[J]. J Allergy Clin Immunol, 2010, 125(2 suppl 2): S33-S40.
[11]	Gazzinelli RT, Hieny S, Wynn TA, et al. Interleukin 12 is required for the T-lymphocyte-independent induction of interferon gamma by an intracellular parasite and induces resistance in T-cell-deficient hosts[J]. Proc Natl Acad Sci U S A, 1993, 90(13): 6115-6119.
[12]	Randow F, MacMicking JD, James LC. Cellular self-defense: how cell-autonomous immunity protects against pathogens[J]. Science, 2013, 340(6133): 701-706. doi: 10.1126/science.1233028 pmid: 23661752
[13]	Chen MX, Sun H, Boot M, et al. Itaconate is an effector of a Rab GTPase cell-autonomous host defense pathway against Salmonella[J]. Science, 2020, 369(6502): 450-455.
[14]	MacMicking JD. Cell-autonomous effector mechanisms against mycobacterium tuberculosis[J]. Cold Spring Harb Perspect Med, 2014, 4(10): a018507.
[15]	Towers GJ, Noursadeghi M. Interactions between HIV-1 and the cell-autonomous innate immune system[J]. Cell Host Microbe, 2014, 16(1): 10-18. doi: 10.1016/j.chom.2014.06.009 pmid: 25011104
[16]	Kousathanas A, Pairo-Castineira E, Rawlik K, et al. Whole-genome sequencing reveals host factors underlying critical COVID-19[J]. Nature, 2022, 607(7917): 97-103.
[17]	Pairo-Castineira E, Rawlik K, Bretherick AD, et al. GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19[J]. Nature, 2023, 617(7962): 764-768.
[18]	Hou YH, Lv FL. The interplay between Toxoplasma gondii infection and autophagy in host cells[J]. Chin J Parasitol Parasit Dis, 2021, 39(4): 537-541, 547. (in Chinese)
	(侯永恒, 吕芳丽. 弓形虫感染与宿主细胞自噬的相互作用[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(4): 537-541, 547.) doi: 10.12140/j.issn.1000-7423.2021.04.019
[19]	Hunter CA, Sibley LD. Modulation of innate immunity by Toxoplasma gondii virulence effectors[J]. Nat Rev Microbiol, 2012, 10(11): 766-778.
[20]	Fujigaki S, Takemura M, Hamakawa H, et al. The mechanism of interferon-gamma induced anti Toxoplasma gondii by indoleamine 2,3-dioxygenase and/or inducible nitric oxide synthase vary among tissues[J]. Adv Exp Med Biol, 2003, 527: 97-103. pmid: 15206721
[21]	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-e01718.
[22]	Zhao YL, Ferguson DJP, Wilson DC, et al. Virulent Toxoplasma gondii evade immunity-related GTPase-mediated parasite vacuole disruption within primed macrophages[J]. J Immunol, 2009, 182(6): 3775-3781.
[23]	Zhao XY, Lempke SL, Urbán Arroyo JC, et al. iNOS is necessary for GBP-mediated T. gondii clearance in murine macrophages via vacuole nitration and intravacuolar network collapse[J]. Nat Commun, 2024, 15(1): 2698.
[24]	Murray HW, Teitelbaum RF. L-arginine-dependent reactive nitrogen intermediates and the antimicrobial effect of activated human mononuclear phagocytes[J]. J Infect Dis, 1992, 165(3): 513-517. pmid: 1538156
[25]	Oberdörfer C, Adams O, MacKenzie CR, et al. Role of IDO activation in anti-microbial defense in human native astrocytes[J]. Adv Exp Med Biol, 2003, 527: 15-26. pmid: 15206712
[26]	Rozenfeld C, Martinez R, Seabra S, et al. Toxoplasma gondii prevents neuron degeneration by interferon-gamma-activated microglia in a mechanism involving inhibition of inducible nitric oxide synthase and transforming growth factor-beta1 production by infected microglia[J]. Am J Pathol, 2005, 167(4): 1021-1031. doi: 10.1016/s0002-9440(10)61191-1 pmid: 16192637
[27]	Dockterman J, Coers J. How did we get here? Insights into mechanisms of immunity-related GTPase targeting to intracellular pathogens[J]. Curr Opin Microbiol, 2022, 69: 102189.
[28]	Martens S, Howard J. The interferon-inducible GTPases[J]. Annu Rev Cell Dev Biol, 2006, 22: 559-589. pmid: 16824009
[29]	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.
[30]	Ohshima J, Lee Y, Sasai MW, 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
[31]	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
[32]	Khaminets A, Hunn JP, Könen-Waisman S, et al. Coordinated loading of IRG resistance GTPases on to the Toxoplasma gondii parasitophorous vacuole[J]. Cell Microbiol, 2010, 12(7): 939-961.
[33]	Yamamoto M, Okuyama M, Ma JS, et al. A cluster of interferon-γ-inducible p65 GTPases plays a critical role in host defense against Toxoplasma gondii[J]. Immunity, 2012, 37(2): 302-313.
[34]	Zhao YO, Könen-Waisman S, Taylor GA, et al. Localisation and mislocalisation of the interferon-inducible immunity-related GTPase, Irgm1 (LRG-47) in mouse cells[J]. PLoS One, 2010, 5(1): e8648.
[35]	Haldar AK, Saka HA, Piro AS, et al. IRG and GBP host resistance factors target aberrant, “non-self” vacuoles characterized by the missing of “self” IRGM proteins[J]. PLoS Pathog, 2013, 9(6): e1003414.
[36]	Maric-Biresev J, Hunn JP, Krut O, et al. Loss of the interferon-γ-inducible regulatory immunity-related GTPase (IRG), Irgm1, causes activation of effector IRG proteins on lysosomes, damaging lysosomal function and predicting the dramatic susceptibility of Irgm1-deficient mice to infection[J]. BMC Biol, 2016, 14: 33. doi: 10.1186/s12915-016-0255-4 pmid: 27098192
[37]	Pradipta A, Sasai MW, Motani K, et al. Cell-autonomous Toxoplasma killing program requires Irgm2 but not its microbe vacuolar localization[J]. Life Sci Alliance, 2021, 4(7): e202000960.
[38]	Zhao YO, Khaminets A, Hunn JP, et al. Disruption of the Toxoplasma gondii parasitophorous vacuole by IFNgamma-inducible immunity-related GTPases (IRG proteins) triggers necrotic cell death[J]. PLoS Pathog, 2009, 5(2): e1000288.
[39]	Hunn JP, Koenen-Waisman S, Papic N, et al. Regulatory interactions between IRG resistance GTPases in the cellular response to Toxoplasma gondii[J]. EMBO J, 2008, 27(19): 2495-2509.
[40]	Martens S, Parvanova I, Zerrahn J, et al. Disruption of Toxoplasma gondii parasitophorous vacuoles by the mouse p47-resistance GTPases[J]. PLoS Pathog, 2005, 1(3): e24. doi: 10.1371/journal.ppat.0010024 pmid: 16304607
[41]	Müller UB, Howard JC. The impact of Toxoplasma gondii on the mammalian genome[J]. Curr Opin Microbiol, 2016, 32: 19-25. doi: S1369-5274(16)30044-3 pmid: 27128504
[42]	MacMicking JD. Interferon-inducible effector mechanisms in cell-autonomous immunity[J]. Nat Rev Immunol, 2012, 12(5): 367-382. doi: 10.1038/nri3210 pmid: 22531325
[43]	Kim BH, Shenoy AR, Kumar P, et al. IFN-inducible GTPases in host cell defense[J]. Cell Host Microbe, 2012, 12(4): 432-444.
[44]	Pilla-Moffett D, Barber MF, Taylor GA, et al. Interferon-inducible GTPases in host resistance, inflammation and disease[J]. J Mol Biol, 2016, 428(17): 3495-3513. doi: 10.1016/j.jmb.2016.04.032 pmid: 27181197
[45]	MacMicking JD. IFN-inducible GTPases and immunity to intracellular pathogens[J]. Trends Immunol, 2004, 25(11): 601-609. doi: 10.1016/j.it.2004.08.010 pmid: 15489189
[46]	Kim BH, Shenoy AR, Kumar P, et al. A family of IFN-γ-inducible 65-kD GTPases protects against bacterial infection[J]. Science, 2011, 332(6030): 717-721.
[47]	Britzen-Laurent N, Bauer M, Berton V, et al. Intracellular trafficking of guanylate-binding proteins is regulated by heterodimerization in a hierarchical manner[J]. PLoS One, 2010, 5(12): e14246.
[48]	Modiano N, Lu YE, Cresswell P. Golgi targeting of human guanylate-binding protein-1 requires nucleotide binding, isoprenylation, and an IFN-gamma-inducible cofactor[J]. Proc Natl Acad Sci USA, 2005, 102(24): 8680-8685. doi: 10.1073/pnas.0503227102 pmid: 15937107
[49]	Fisch D, Bando H, Clough B, et al. Human GBP1 is a microbe-specific gatekeeper of macrophage apoptosis and pyroptosis[J]. EMBO J, 2019, 38(13): e100926.
[50]	Qin AP, Lai DH, Liu QF, et al. Guanylate-binding protein 1 (GBP1) contributes to the immunity of human mesenchymal stromal cells against Toxoplasma gondii[J]. Proc Natl Acad Sci U S A, 2017, 114(6): 1365-1370.
[51]	Fisch D, Pfleiderer MM, Anastasakou E, et al. PIM1 controls GBP1 activity to limit self-damage and to guard against pathogen infection[J]. Science, 2023, 382(6666): eadg2253.
[52]	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.
[53]	Sun HY, Yu D, Kong FL, et al. Regulatory effect of ubiquitin-proteasome system in growth and development of parasitic Protozoa and analysis of potential drug targets[J]. J Jilin Med Univ, 2024, 45(4): 286-290, 295. (in Chinese)
	(孙宏宇, 于丹, 孔繁利, 等. 泛素-蛋白酶体系统在寄生原虫生长发育中的调控作用及潜在药物靶点分析[J]. 吉林医药学院学报, 2024, 45(4): 286-290, 295.)
[54]	Clough B, Fisch D, Mize TH, et al. p97/VCP targets Toxoplasma gondii vacuoles for parasite restriction in interferon-stimulated human cells[J]. mSphere, 2023, 8(6): e0051123.
[55]	Haldar AK, Foltz C, Finethy R, et al. Ubiquitin systems mark pathogen-containing vacuoles as targets for host defense by guanylate binding proteins[J]. Proc Natl Acad Sci USA, 2015, 112(41): E5628-E5637.
[56]	Lee Y, Sasai MW, Ma JS, et al. p62 plays a specific role in interferon-γ-induced presentation of a Toxoplasma vacuolar antigen[J]. Cell Rep, 2015, 13(2): 223-233.
[57]	Lee Y, Yamada H, Pradipta A, et al. Initial phospholipid-dependent Irgb6 targeting to Toxoplasma gondii vacuoles mediates host defense[J]. Life Sci Alliance, 2020, 3(1): e201900549.
[58]	Wang YF, Hollingsworth LR, Sangaré LO, et al. Host E3 ubiquitin ligase ITCH mediates Toxoplasma gondii effector GRA35-triggered NLRP1 inflammasome activation and cell-autonomous immunity[J]. mBio, 2024, 15(3): e0330223.
[59]	Mukhopadhyay D, Sangaré LO, Braun L,et al. Toxoplasma GRA15 limits parasite growth in IFNγ-activated fibroblasts through TRAF ubiquitin ligases[J]. EMBO J, 2020, 39(10): e103758.
[60]	Saeij JP, Boyle JP, Coller S, et al. Polymorphic secreted kinases are key virulence factors in toxoplasmosis[J]. Science, 2006, 314(5806): 1780-1783. doi: 10.1126/science.1133690 pmid: 17170306
[61]	Taylor S, Barragan A, Su C, et al. A secreted serine-threonine kinase determines virulence in the eukaryotic pathogen Toxoplasma gondii[J]. Science, 2006, 314(5806): 1776-1780. doi: 10.1126/science.1133643 pmid: 17170305
[62]	Clough B, Wright JD, Pereira PM, et al. K63-Linked ubiquitination targets Toxoplasma gondii for Endo-lysosomal destruction in IFNγ-stimulated human cells[J]. PLoS Pathog, 2016, 12(11): e1006027.
[63]	Dittmar G, Winklhofer KF. Linear ubiquitin chains: cellular functions and strategies for detection and quantification[J]. Front Chem, 2019, 7: 915. doi: 10.3389/fchem.2019.00915 pmid: 31998699
[64]	Hernandez D, Walsh S, Saavedra Sanchez L, et al. Interferon-inducible E3 ligase RNF213 facilitates host-protective linear and K63-linked ubiquitylation of Toxoplasma gondii parasitophorous vacuoles[J]. mBio, 2022, 13(5): e0188822.
[65]	Krishnamurthy S, Konstantinou EK, Young LH, et al. The human immune response to Toxoplasma: autophagy versus cell death[J]. PLoS Pathog, 2017, 13(3): e1006176.
[66]	Mizushima N, Yoshimori T, Ohsumi Y. The role of Atg proteins in autophagosome formation[J]. Annu Rev Cell Dev Biol, 2011, 27: 107-132. doi: 10.1146/annurev-cellbio-092910-154005 pmid: 21801009
[67]	Choi J, Park S, Biering SB, et al. The parasitophorous vacuole membrane of Toxoplasma gondii is targeted for disruption by ubiquitin-like conjugation systems of autophagy[J]. Immunity, 2014, 40(6): 924-935.
[68]	Wacker R, Eickel N, Schmuckli-Maurer J, et al. LC3-association with the parasitophorous vacuole membrane of Plasmodium berghei liver stages follows a noncanonical autophagy pathway[J]. Cell Microbiol, 2017, 19(10)
[69]	Zhao ZJ, 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
[70]	Bhushan J, Radke JB, Perng YC, et al. ISG15 connects autophagy and IFN-γ-dependent control of Toxoplasma gondii infection in human cells[J]. mBio, 2020, 11(5): e00852-20.
[71]	Wu MM, An R, Zhou N,et al. Toxoplasma gondii CDPK3 controls the intracellular proliferation of parasites in macrophages[J]. Front Immunol, 2022, 13: 905142.
[72]	Randow F, Münz C. Autophagy in the regulation of pathogen replication and adaptive immunity[J]. Trends Immunol, 2012, 33(10): 475-487. doi: 10.1016/j.it.2012.06.003 pmid: 22796170
[73]	Pillich H, Chakraborty T, Mraheil MA. Cell-autonomous responses in Listeria monocytogenes infection[J]. Future Microbiol, 2015, 10(4): 583-597. doi: 10.2217/fmb.15.4 pmid: 25865195
[74]	Könen-Waisman S, Howard JC. Cell-autonomous immunity to Toxoplasma gondii in mouse and man[J]. Microbes Infect, 2007, 9(14/15): 1652-1661.