Abstract
Toxoplasma gondii is a pathogenic protozoan parasite belonging to the apicomplexan phylum that infects the nucleated cells of warm-blooded hosts leading to an infectious disease known as toxoplasmosis. Apicomplexan parasites such as T. gondii can display different mechanisms to control or manipulate host cells signaling at different levels altering the host subcellular genome and proteome. Indeed, Toxoplasma is able to modulate host cell responses (especially immune responses) during infection to its advantage through both structural and functional changes in the proteome of different infected cells. Consequently, parasites can transform the invaded cells into a suitable environment for its own replication and the induction of infection. Proteomics as an applicable tool can identify such critical proteins involved in pathogen (Toxoplasma)-host cell interactions and consequently clarify the cellular mechanisms that facilitate the entry of pathogens into host cells, and their replication and transmission, as well as the central mechanisms of host defense against pathogens. Accordingly, the current paper reviews several proteins (identified using proteomic approaches) differentially expressed in the proteome of Toxoplasma-infected host cells (macrophages and human foreskin fibroblasts) and tissues (brain and liver) and highlights their plausible functions in the cellular biology of the infected cells. The identification of such modulated proteins and their related cell impact (cell responses/signaling) can provide further information regarding parasite pathogenesis and biology that might lead to a better understanding of therapeutic strategies and novel drug targets.
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Abreu R, Giri P, Quinn F (2020) Host-pathogen interaction as a novel target for host-directed therapies in tuberculosis. Front Immunol 11:1553
Adomako-Ankomah Y et al (2016) Host mitochondrial association evolved in the human parasite Toxoplasma gondii via neofunctionalization of a gene duplicate. Genetics 203(1):283–298
Ahn H-J, Kim JY, Ryu K-J, Nam H-W (2009) STAT6 activation by Toxoplasma gondii infection induces the expression of Th2 CC chemokine ligands and B clade serine protease inhibitors in macrophage. Parasitol Res 105(5):1445–1453
Al-Bajalan MM, Xia D, Armstrong S, Randle N, Wastling JM (2017) Toxoplasma gondii and Neospora caninum induce different host cell responses at proteome-wide phosphorylation events; a step forward for uncovering the biological differences between these closely related parasites. Parasitol Res 116(10):2707–2719
Alves E et al (2021) An extracellular redox signal triggers calcium release and impacts the asexual development of Toxoplasma gondii. Front Cell Infect Microbiol 11:728425
Attias M, Teixeira DE, Benchimol M, Vommaro RC, Crepaldi PH, De Souza W (2020) The life-cycle of Toxoplasma gondii reviewed using animations. Parasit Vectors 13(1):588
Bando H et al (2018) Toxoplasma effector TgIST targets host IDO1 to antagonize the IFN-γ-induced anti-parasitic response in human cells. Front Immunol 9:2073
Bayani M, Riahi SM, Bazrafshan N, Gamble HR, Rostami A (2019) Toxoplasma gondii infection and risk of Parkinson and Alzheimer diseases: a systematic review and meta-analysis on observational studies. Acta Trop 196:165–171
Bennett AP, Robinson MW (2021) Trematode proteomics: recent advances and future directions. Pathogens 10(3):348
Bergersen KV, Barnes A, Worth D, David C, Wilson EH (2021) Targeted transcriptomic analysis of C57BL/6 and BALB/c mice during progressive chronic Toxoplasma gondii infection reveals changes in host and parasite gene expression relating to neuropathology and resolution. Front Cell Infect Microbiol 11:645778
Besteiro S (2019) The role of host autophagy machinery in controlling Toxoplasma infection. Virulence 10(1):438–447
Bichiou H, Bouabid C, Rabhi I, Guizani-Tabbane L (2021) Transcription factors interplay orchestrates the immune-metabolic response of Leishmania infected macrophages. Front Cell Infect Microbiol 11:660415
Bisio H et al (2020) The ZIP code of vesicle trafficking in Apicomplexa: SEC1/Munc18 and SNARE proteins. MBio 11(5):e02092–e02020
Blank ML et al (2018) A Toxoplasma gondii locus required for the direct manipulation of host mitochondria has maintained multiple ancestral functions. Mol Microbiol 108(5):519–535
Blank ML et al (2021) Toxoplasma gondii association with host mitochondria requires key mitochondrial protein import machinery. Proc Natl Acad Sci U S A 118(12):e2013336118
Borah K, Xu Y, McFadden J (2021) Dissecting host-pathogen interactions in TB using systems-based omic approaches. Front Immunol 12:762315
Butcher BA et al (2011) Toxoplasma gondii rhoptry kinase ROP16 activates STAT3 and STAT6 resulting in cytokine inhibition and arginase-1-dependent growth control. PLoS Pathog 7(9):e1002236
Cabral CM et al (2016) Neurons are the primary target cell for the brain-tropic intracellular parasite Toxoplasma gondii. PLoS Pathog 12(2):e1005447
Castillo C et al (2013) The interaction of classical complement component C1 with parasite and host calreticulin mediates Trypanosoma cruzi infection of human placenta. PLoS Negl Trop Dis 7(8):e2376
Chadee K, Chadha A (2021) The NF-κB pathway: modulation by Entamoeba histolytica and other Protozoan parasites. Front Cell Infect Microbiol 11:748404
Chen J et al (2021) Annexin A1 attenuates cardiac diastolic dysfunction in mice with inflammatory arthritis. Proc Natl Acad Sci U S A 118(38):e2020385118
Coffey MJ et al (2018) Aspartyl protease 5 matures dense granule proteins that reside at the host-parasite interface in Toxoplasma gondii. MBio 9(5):e01796–e01718
Cuervo P, Padron G (2021) Proteomics studies on Protozoan Parasite Biology. J Proteome 248:104346
Cygan AM et al (2021) Proximity-labeling reveals novel host and parasite proteins at the Toxoplasma parasitophorous vacuole membrane. Mbio 12(6):e00260–e00221
Damasceno-Sá JC et al (2021) Inhibition of nitric oxide production of activated mice peritoneal macrophages is independent of the Toxoplasma gondii strain. Mem Inst Oswaldo Cruz 116:e200417
de Oliveira Cardoso MF et al (2018) Annexin A1 peptide is able to induce an anti-parasitic effect in human placental explants infected by Toxoplasma gondii. Microb Pathog 123:153–161
de Souza W, Barrias ES (2020) Membrane-bound extracellular vesicles secreted by parasitic protozoa: cellular structures involved in the communication between cells. Parasitol Res 119(7):2005–2023
Dogga SK et al (2017) A druggable secretory protein maturase of Toxoplasma essential for invasion and egress. Elife 6:e27480
Du J et al (2014) Toxoplasma gondii virulence factor ROP18 inhibits the host NF-κB pathway by promoting p65 degradation. J Biol Chem 289(18):12578–12592
Dubey JP (2020) The history and life cycle of Toxoplasma gondii. In: Toxoplasma gondii, 3rd edn. Elsevier, pp 1–19
Forman HJ, Zhang H (2021) Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. Nat Rev Drug Discov 20(9):689–709
Freudenberg F, Celikel T, Reif A (2015) The role of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in depression: central mediators of pathophysiology and antidepressant activity? Neurosci Biobehav Rev 52:193–206
Frickel E-M, Hunter CA (2021) Lessons from Toxoplasma: Host responses that mediate parasite control and the microbial effectors that subvert them. J Exp Med 218(11):e20201314
Fulda S (2013) How to target apoptosis signaling pathways for the treatment of pediatric cancers. Front Oncol 3:22
Gaji RY, Sharp AK, Brown AM (2021) Protein kinases in Toxoplasma gondii. Int J Parasitol 51(6):415–429
Gibson LL, McKeever A, Coutinho E, Finke C, Pollak T (2020) Cognitive impact of neuronal antibodies: encephalitis and beyond. Transl Psychiatry 10(1):304
Gigley JP, Fox BA, Bzik DJ (2009) Cell-mediated immunity to Toxoplasma gondii develops primarily by local Th1 host immune responses in the absence of parasite replication. J Immunol 182(2):1069–1078
Haas P, Muralidharan M, Krogan NJ, Kaake RM, Hüttenhain R (2021) Proteomic approaches to study SARS-CoV-2 biology and COVID-19 pathology. J Proteome Res 20(2):1133–1152
Hamie M et al (2021) Imiquimod targets toxoplasmosis through modulating host toll-like receptor-MyD88 signaling. Front Immunol 12:629917
Hayashi N, Peacock J, Beraldi E, Zoubeidi A, Gleave M, Ong C (2012) Hsp27 silencing coordinately inhibits proliferation and promotes Fas-induced apoptosis by regulating the PEA-15 molecular switch. Cell Death Differ 19(6):990–1002
He J-J, Ma J, Elsheikha HM, Song H-Q, Zhou D-H, Zhu X-Q (2016) Proteomic profiling of mouse liver following acute Toxoplasma gondii infection. PLoS One 11(3):e0152022
He C, Kong L, Puthiyakunnon S, Wei H-X, Zhou L-J, Peng H-J (2019) iTRAQ-based phosphoproteomic analysis reveals host cell's specific responses to Toxoplasma gondii at the phases of invasion and prior to egress. Biochim Biophys Acta, Proteins Proteomics 1867(3):202–212
He J-J et al (2020) iTRAQ-based quantitative proteomics analysis identifies host pathways modulated during Toxoplasma gondii infection in swine. Microorganisms 8(4):518
Herbison R, Evans S, Doherty J-F, Algie M, Kleffmann T, Poulin R (2019) A molecular war: convergent and ontogenetic evidence for adaptive host manipulation in related parasites infecting divergent hosts. Proc Biol Sci 286(1915):20191827
Hermanns T, Müller UB, Könen-Waisman S, Howard JC, Steinfeldt T (2016) The Toxoplasma gondii rhoptry protein ROP18 is an Irga6-specific kinase and regulated by the dense granule protein GRA7. Cell Microbiol 18(2):244–259
Herneisen AL, Sidik SM, Markus BM, Drewry DH, Zuercher WJ, Lourido S (2020) Identifying the target of an antiparasitic compound in Toxoplasma using thermal proteome profiling. ACS Chem Biol 15(7):1801–1807
Hlaváčová J, Flegr J, Fiurašková K, Kaňková Š (2021) Relationship between latent toxoplasmosis and depression in clients of a center for assisted reproduction. Pathogens 10(8):1052
Holtz A, Basisty N, Schilling B (2021) Quantification and identification of post-translational modifications using modern proteomics approaches. Methods Mol Biol 2228:225–235
Hu X, O’shaughnessy WJ, Beraki TG, Reese ML (2020) Loss of the conserved alveolate kinase MAPK2 decouples Toxoplasma cell growth from cell division. Mbio 11(6):e02517–e02520
Jin D-Y, Chae HZ, Rhee SG, Jeang K-T (1997) Regulatory role for a novel human thioredoxin peroxidase in NF-κB activation. J Biol Chem 272(49):30952–30961
Jo SH et al (2017) Calreticulin modulates the intracellular survival of mycobacteria by regulating ER-stress-mediated apoptosis. Oncotarget 8(35):58686–58698
Kannan G et al (2017) Pathogen-mediated NMDA receptor autoimmunity and cellular barrier dysfunction in schizophrenia. Transl Psychiatry 7(8):e1186–e1186
Kelly FD, Wei BM, Cygan AM, Parker ML, Boulanger MJ, Boothroyd JC (2017) Toxoplasma gondii MAF1b binds the host cell MIB complex to mediate mitochondrial association. Msphere 2(3):e00183–e00117
Khan A, Grigg ME (2017) Toxoplasma gondii: laboratory maintenance and growth. Curr Protoc Microbiol 44(1):20C:1.1-20C. 1.17
Kim K et al (2011) Role of excitatory amino acid transporter-2 (EAAT2) and glutamate in neurodegeneration: opportunities for developing novel therapeutics. J Cell Physiol 226(10):2484–2493
Kim H-J et al (2020) Secretome analysis of host cells infected with Toxoplasma gondii after treatment of human epidermal growth factor receptor 2/4 inhibitors. Korean J Parasitol 58(3):249–255
Kong L et al (2020) Tg ROP18 targets IL20RB for host-defense-related-STAT3 activation during Toxoplasma gondii infection. Parasit Vectors 13(1):400
Kravets E et al (2016) Guanylate binding proteins directly attack Toxoplasma gondii via supramolecular complexes. Elife 5:e11479
Kreimendahl S, Rassow J (2020) The mitochondrial outer membrane protein Tom70-mediator in protein traffic, membrane contact sites and innate immunity. Int J Mol Sci 21(19):7262
Kumar A (2021a) Proteomics in host-protozoan parasite interactions and development of drug and vaccine. Adv Pharm Bull 11(2):209–211
Kumar V (2021b) Can proteomics-based approaches further help COVID-19 prevention and therapy? Expert Rev Proteomics 18(4):241–245
Lang D et al (2018) Chronic Toxoplasma infection is associated with distinct alterations in the synaptic protein composition. J Neuroinflammation 15(1):216
Lanneau D, de Thonel A, Maurel S, Didelot C, Garrido C (2007) Apoptosis versus cell differentiation: role of heat shock proteins HSP90, HSP70 and HSP27. Prion 1(1):53–60
Lathe R, Sapronova A, Kotelevtsev Y (2014) Atherosclerosis and Alzheimer-diseases with a common cause? Inflammation, oxysterols, vasculature. BMC Geriatr 14:36
Leal-Sena JA et al (2018) Toxoplasma gondii antigen SAG2A differentially modulates IL-1β expression in resistant and susceptible murine peritoneal cells. Appl Microbiol Biotechnol 102(5):2235–2249
Li Z et al (2012) Differences in iNOS and arginase expression and activity in the macrophages of rats are responsible for the resistance against T. gondii infection. PLoS One 7(4):e35834
Li C et al (2018a) Regulation of Staphylococcus aureus infection of macrophages by CD44, reactive oxygen species, and acid sphingomyelinase. Antioxid Redox Signal 28(10):916–934
Li Y et al (2018b) Chronic Toxoplasma gondii infection induces anti-N-methyl-d-aspartate receptor autoantibodies and associated behavioral changes and neuropathology. Infect Immun 86(10):e00398–e00318
Li C-W, Li L-L, Chen S, Zhang J-X, Lu W-L (2020a) Antioxidant nanotherapies for the treatment of inflammatory diseases. Front Bioeng Biotechnol 8:200
Li S et al (2020b) Comparative transcriptome analysis of normal and CD44-deleted mouse brain under chronic infection with Toxoplasma gondii. Acta Trop 210:105589
Li X et al (2022) Mitochondria shed their outer membrane in response to infection-induced stress. Science 375(6577):eabi4343
Liu Q, Wang Z-D, Huang S-Y, Zhu X-Q (2015) Diagnosis of toxoplasmosis and typing of Toxoplasma gondii. Parasit Vectors 8:292
Lum KK, Cristea IM (2016) Proteomic approaches to uncovering virus-host protein interactions during the progression of viral infection. Expert Rev Proteomics 13(3):325–340
Macêdo AG et al (2013) SAG2A protein from Toxoplasma gondii interacts with both innate and adaptive immune compartments of infected hosts. Parasit Vectors 6:163
Malik AR, Willnow TE (2019) Excitatory amino acid transporters in physiology and disorders of the central nervous system. Int J Mol Sci 20(22):5671
Mammari N, Halabi MA, Yaacoub S, Chlala H, Dardé M-L, Courtioux B (2019) Toxoplasma gondii modulates the host cell responses: an overview of apoptosis pathways. Biomed Res Int 2019:1–10
Mansouri R et al (2020) The use of proteomics for the identification of promising vaccine and diagnostic biomarkers in Plasmodium falciparum. Parasitology 147(12):1255–1262
Mantovani A, Dinarello CA, Molgora M, Garlanda C (2019) Interleukin-1 and related cytokines in the regulation of inflammation and immunity. Immunity 50(4):778–795
Marcus K, Rabilloud T (2020) How do the different proteomic strategies cope with the complexity of biological regulations in a multi-omic world? Critical appraisal and suggestions for improvements. Proteomes 8(3):23
Mayorova MA, Butoma BG, Churilov LP, Gilburd B, Petrova NN, Shoenfeld Y (2021) Autoimmune concept of schizophrenia: historical roots and current facets. Psychiatr Danub 33(1):3–17
Meier RP et al (2019) Interleukin-1 receptor antagonist modulates liver inflammation and fibrosis in mice in a model-dependent manner. Int J Mol Sci 20(6):1295
Mendez OA, Machado EF, Lu J, Koshy AA (2021) Injection with Toxoplasma gondii protein affects neuron health and survival. Elife 10:e67681
Miao M et al (2019) Proteomics profiling of host cell response via protein expression and phosphorylation upon dengue virus infection. Virol Sin 34(5):549–562
Mimura KK, Tedesco RC, Calabrese KS, Gil CD, Oliani SM (2012) The involvement of anti-inflammatory protein, annexin A1, in ocular toxoplasmosis. Mol Vis 18:1583–1593
Monroy-Ramirez HC, Galicia-Moreno M, Sandoval-Rodriguez A, Meza-Rios A, Santos A, Armendariz-Borunda J (2021) PPARs as metabolic sensors and therapeutic targets in liver diseases. Int J Mol Sci 22(15):8298
Moumen A, Masterson P, O'Connor MJ, Jackson SP (2005) hnRNP K: an HDM2 target and transcriptional coactivator of p53 in response to DNA damage. Cell 123(6):1065–1078
Mouveaux T et al (2021) Primary brain cell infection by Toxoplasma gondii reveals the extent and dynamics of parasite differentiation and its impact on neuron biology. Open Biol 11(10):210053
Mukherjee A, Verma A, Bihani S, Burli A, Mantri K, Srivastava S (2021) Proteomics advances towards developing SARS-CoV-2 therapeutics using in silico drug repurposing approaches. Drug Discov Today Technol 39:1–12
Nakazawa K, Sapkota K (2020) The origin of NMDA receptor hypofunction in schizophrenia. Pharmacol Ther 205:107426
Nasirpour S, Kheirandish F, Fallahi S (2020) Depression and Toxoplasma gondii infection: assess the possible relationship through a seromolecular case-control study. Arch Microbiol 202(10):2689–2695
Nayeri T, Sarvi S, Sharif M, Daryani A (2021) Toxoplasma gondii: a possible etiologic agent for Alzheimer's disease. Heliyon 7(6):e07151
Nelson M, Jones A, Carmen J, Sinai A, Burchmore R, Wastling J (2008) Modulation of the host cell proteome by the intracellular apicomplexan parasite Toxoplasma gondii. Infect Immun 76(2):828–844
Ngo CC, Man SM (2017) Mechanisms and functions of guanylate-binding proteins and related interferon-inducible GTPases: roles in intracellular lysis of pathogens. Cell Microbiol 19(12):e12791
Nissilä E et al (2018) Complement factor H and apolipoprotein E participate in regulation of inflammation in THP-1 macrophages. Front Immunol 9:2701
Noguchi A et al (2021) Decreased lamin B1 levels affect gene positioning and expression in postmitotic neurons. Neurosci Res 173:22–33
Olias P, Etheridge RD, Zhang Y, Holtzman MJ, Sibley LD (2016) Toxoplasma effector recruits the Mi-2/NuRD complex to repress STAT1 transcription and block IFN-γ-dependent gene expression. Cell Host Microbe 20(1):72–82
Ortiz-Guerrero G, Gonzalez-Reyes RE, de-la Torre A, Medina-Rincón G, Nava-Mesa MO (2020) Pathophysiological mechanisms of cognitive impairment and neurodegeneration by Toxoplasma gondii infection. Brain Sci 10(6):369
Park J, Hunter CA (2020) The role of macrophages in protective and pathological responses to Toxoplasma gondii. Parasite Immunol 42(7):e12712
Parkin GM, Udawela M, Gibbons A, Dean B (2018) Glutamate transporters, EAAT1 and EAAT2, are potentially important in the pathophysiology and treatment of schizophrenia and affective disorders. World J Psychiatry 8(2):51–63
Pascovici D et al (2019) Clinically relevant post-translational modification analyses-maturing workflows and bioinformatics tools. Int J Mol Sci 20(1):16
Pernas L et al (2014) Toxoplasma effector MAF1 mediates recruitment of host mitochondria and impacts the host response. PLoS Biol 12(4):e1001845
Portillo J-AC et al (2017) Toxoplasma gondii induces FAK-Src-STAT3 signaling during infection of host cells that prevents parasite targeting by autophagy. PLoS Pathog 13(10):e1006671
Praefcke GJ (2018) Regulation of innate immune functions by guanylate-binding proteins. Int J Mol Sci 308(1):237–245
Proksova M, Rehulkova H, Rehulka P, Lays C, Lenco J, Stulik J (2020) Using proteomics to identify host cell interaction partners for VgrG and IglJ. Sci Rep 10(1):14612
Quevedo MC, Cruz AH, Contreras AJD (2019) Relationship between biology, immune response and clinical characteristics in Toxoplasma gondii infection. Rev Cubana Invest Biomed 38(4):e256
Rahmatbakhsh M, Gagarinova A, Babu M (2021) Bioinformatic analysis of temporal and spatial proteome alternations during infections. Front Genet 12:667936
Ramirez Rios S et al (2021) A proteomic-informed view of the changes induced by loss of cellular adherence: the example of mouse macrophages. PLoS One 16(5):e0252450
Ramírez G et al (2012) Roles of Trypanosoma cruzi calreticulin in parasite-host interactions and in tumor growth. Mol Immunol 52(3-4):133–140
Rashidi S, Nguewa P, Mojtahedi Z, Shahriari B, Kalantar K, Hatam G (2020) Identification of immunoreactive proteins in secretions of Leishmania infantum promastigotes: an immunoproteomic approach. East Mediterr Health J 26(12):1548–1555
Rashidi S et al (2021a) The host mTOR pathway and parasitic diseases pathogenesis. Parasitol Res 120(4):1151–1166
Rashidi S et al (2021b) The main post-translational modifications and related regulatory pathways in the malaria parasite Plasmodium falciparum: An update. J Proteome 245:104279
Rosenberg A, Sibley LD (2021) Toxoplasma gondii secreted effectors co-opt host repressor complexes to inhibit necroptosis. Cell Host Microbe 29(7):1186–1198. e8
Rosowski EE et al (2011) Strain-specific activation of the NF-κB pathway by GRA15, a novel Toxoplasma gondii dense granule protein. J Exp Med 208(1):195–212
Saeij JP, Frickel E-M (2017) Exposing Toxoplasma gondii hiding inside the vacuole: a role for GBPs, autophagy and host cell death. Curr Opin Microbiol 40:72–80
Saez A, Herrero-Fernandez B, Gomez-Bris R, Somovilla-Crespo B, Rius C, Gonzalez-Granado JM (2020) Lamin A/C and the immune system: one intermediate filament, many faces. Int J Mol Sci 21(17):6109
Sangaré LO et al (2019) Toxoplasma GRA15 activates the NF-κB pathway through interactions with TNF receptor-associated factors. MBio 10(4):e00808–e00819
Santana SS et al (2012) Analysis of IgG subclasses (IgG1 and IgG3) to recombinant SAG2A protein from Toxoplasma gondii in sequential serum samples from patients with toxoplasmosis. Immunol Lett 143(2):193–201
Santana BB et al (2021) Low Annexin A1 level in HTLV-1 infected patients is a potential biomarker for the clinical progression and diagnosis of HAM/TSP. BMC Infect Dis 21(1):219
Selleck EM et al (2013) Guanylate-binding protein 1 (Gbp1) contributes to cell-autonomous immunity against Toxoplasma gondii. PLoS Pathog 9(4):e1003320
Seternes O-M, Kidger AM, Keyse SM (2019) Dual-specificity MAP kinase phosphatases in health and disease. Biochim Biophys Acta, Mol Cell Res 1866(1):124–143
Shaw MK, Roos DS, Tilney LG (2002) Cysteine and serine protease inhibitors block intracellular development and disrupt the secretory pathway of Toxoplasma gondii. Microbes Infect 4(2):119–132
Sidik SM et al (2016) A genome-wide CRISPR screen in Toxoplasma identifies essential apicomplexan genes. Cell 166(6):1423–1435. e12
Smith NC, Goulart C, Hayward JA, Kupz A, Miller CM, van Dooren GG (2021) Control of human toxoplasmosis. Int J Parasitol 51(2-3):95–121
Sperk M et al (2020) Utility of proteomics in emerging and re-emerging infectious diseases caused by RNA viruses. J Proteome Res 19(11):4259–4274
Stolf BS et al (2011) Protein disulfide isomerase and host-pathogen interaction. ScientificWorldJournal 11:1749–1761
Stryiński R, Łopieńska-Biernat E, Carrera M (2020) Proteomic insights into the biology of the most important foodborne parasites in Europe. Foods 9(10):1403
Stutz A, Kessler H, Kaschel M-E, Meissner M, Dalpke AH (2012) Cell invasion and strain dependent induction of suppressor of cytokine signaling-1 by Toxoplasma gondii. Immunobiology 217(1):28–36
Sullivan WJ Jr, Jeffers V (2012) Mechanisms of Toxoplasma gondii persistence and latency. FEMS Microbiol Rev 36(3):717–733
Sun H et al (2021) Comparative proteomics analysis for elucidating the interaction between host cells and Toxoplasma gondii. Front Cell Infect Microbiol 11:643001
Swierzy IJ et al (2017) Divergent co-transcriptomes of different host cells infected with Toxoplasma gondii reveal cell type-specific host-parasite interactions. Sci Rep 7(1):7229
Szewczyk-Golec K, Pawłowska M, Wesołowski R, Wróblewski M, Mila-Kierzenkowska C (2021) Oxidative stress as a possible target in the treatment of toxoplasmosis: perspectives and ambiguities. Int J Mol Sci 22(11):5705
Tomita T, Guevara RB, Shah LM, Afrifa AY, Weiss LM (2021) Secreted effectors modulating immune responses to Toxoplasma gondii. Life 11(9):988
Treccani G, Gaarn du Jardin K, Wegener G, Müller HK (2016) Differential expression of postsynaptic NMDA and AMPA receptor subunits in the hippocampus and prefrontal cortex of the flinders sensitive line rat model of depression. Synapse 70(11):471–474
Wang Y et al (2020) Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages. Nat Commun 11(1):5258
Witola WH et al (2014) ALOX12 in human toxoplasmosis. Infect Immun 82(7):2670–2679
Wong ZS, Borrelli SLS, Coyne CC, Boyle JP (2020) Cell type-and species-specific host responses to Toxoplasma gondii and its near relatives. Int J Parasitol 50(5):423–431
Woods S, Schroeder J, McGachy HA, Plevin R, Roberts CW, Alexander J (2013) MAP kinase phosphatase-2 plays a key role in the control of infection with Toxoplasma gondii by modulating iNOS and arginase-1 activities in mice. PLoS Pathog 9(8):e1003535
Xia J et al (2018) Genome-wide bimolecular fluorescence complementation-based proteomic analysis of Toxoplasma gondii ROP18’s human interactome shows its key role in regulation of cell immunity and apoptosis. Front Immunol 9:61
Xiao Z, Ko HL, Goh EH, Wang B, Ren EC (2013) hnRNP K suppresses apoptosis independent of p53 status by maintaining high levels of endogenous caspase inhibitors. Carcinogenesis 34(7):1458–1467
Xue J et al (2017) Thioredoxin reductase from Toxoplasma gondii: an essential virulence effector with antioxidant function. FASEB J 31(10):4447–4457
Yahya RS, Awad SI, El-Baz HA, Saudy N, Abdelsalam OA, Al-Din MSS (2017) Impact of ApoE genotypes variations on Toxoplasma patients with dementia. J Clin Neurosci 39:184–188
Yang J et al (2018) Brain proteomic differences between wild-type and CD44-mice induced by chronic Toxoplasma gondii infection. Parasitol Res 117(8):2623–2633
Yao L et al (2021) Toxoplasma gondii Type-I ROP18 targeting human E3 ligase TRIM21 for immune escape. Front Cell Dev Biol 9:685913
Young J et al (2019) A CRISPR platform for targeted in vivo screens identifies Toxoplasma gondii virulence factors in mice. Nat Commun 10(1):3963
Zhang Z-W et al (2020) Functional characterization of two thioredoxin proteins of Toxoplasma gondii using the CRISPR-Cas9 system. Front Vet Sci 7:614759
Zhao Z-J et al (2013) Lower expression of inducible nitric oxide synthase and higher expression of arginase in rat alveolar macrophages are linked to their susceptibility to Toxoplasma gondii infection. PLoS One 8(5):e63650
Zhao S, Feng J, Wang Q, Tian L, Zhang Y, Li H (2018) hnRNP K plays a protective role in TNF-α-induced apoptosis in podocytes. Biosci Rep 38(3):BSR20180288
Zheng Z, Li Y, Jin G, Huang T, Zou M, Duan S (2020) The biological role of arachidonic acid 12-lipoxygenase (ALOX12) in various human diseases. Biomed Pharmacother 129:110354
Zhou D et al (2011) Modulation of mouse macrophage proteome induced by Toxoplasma gondii tachyzoites in vivo. Parasitol Res 109(6):1637–1646
Zhou D-H et al (2013) Changes in the proteomic profiles of mouse brain after infection with cyst-forming Toxoplasma gondii. Parasit Vectors 6(1):96
Zhou L-J et al (2019) Toxoplasma gondii ROP18 inhibits human glioblastoma cell apoptosis through a mitochondrial pathway by targeting host cell P2X1. Parasit Vectors 12:284
Zhou C-X, Gao M, Han B, Cong H, Zhu X-Q, Zhou H-Y (2021) Quantitative peptidomics of mouse brain after infection with cyst-forming Toxoplasma gondii. Front Immunol 12:681242
Zhu W, Li J, Pappoe F, Shen J, Yu L (2019) Strategies developed by Toxoplasma gondii to survive in the host. Front Microbiol 10:899
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PN gratefully acknowledges the support provided by Fundación La Caixa (LCF/PR/PR13/51080005) and Fundación Caja Navarra, Fundación Roviralta, Ubesol, and COST actions CA18217 (ENOVAT) and CA18218. We acknowledge Prof. Paul Miller (PhD) from the University of Navarra for language editing.
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Rashidi, S., Vieira, C., Mansouri, R. et al. Host cell proteins modulated upon Toxoplasma infection identified using proteomic approaches: a molecular rationale. Parasitol Res 121, 1853–1865 (2022). https://doi.org/10.1007/s00436-022-07541-4
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DOI: https://doi.org/10.1007/s00436-022-07541-4