Skip to main content

Advertisement

Log in

Host cell proteins modulated upon Toxoplasma infection identified using proteomic approaches: a molecular rationale

  • Immunology and Host-Parasite Interactions - Review
  • Published:
Parasitology Research Aims and scope Submit manuscript

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.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Abreu R, Giri P, Quinn F (2020) Host-pathogen interaction as a novel target for host-directed therapies in tuberculosis. Front Immunol 11:1553

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Bennett AP, Robinson MW (2021) Trematode proteomics: recent advances and future directions. Pathogens 10(3):348

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Besteiro S (2019) The role of host autophagy machinery in controlling Toxoplasma infection. Virulence 10(1):438–447

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bisio H et al (2020) The ZIP code of vesicle trafficking in Apicomplexa: SEC1/Munc18 and SNARE proteins. MBio 11(5):e02092–e02020

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Borah K, Xu Y, McFadden J (2021) Dissecting host-pathogen interactions in TB using systems-based omic approaches. Front Immunol 12:762315

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cabral CM et al (2016) Neurons are the primary target cell for the brain-tropic intracellular parasite Toxoplasma gondii. PLoS Pathog 12(2):e1005447

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chadee K, Chadha A (2021) The NF-κB pathway: modulation by Entamoeba histolytica and other Protozoan parasites. Front Cell Infect Microbiol 11:748404

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • Cuervo P, Padron G (2021) Proteomics studies on Protozoan Parasite Biology. J Proteome 248:104346

    Article  CAS  Google Scholar 

  • Cygan AM et al (2021) Proximity-labeling reveals novel host and parasite proteins at the Toxoplasma parasitophorous vacuole membrane. Mbio 12(6):e00260–e00221

    Article  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Dogga SK et al (2017) A druggable secretory protein maturase of Toxoplasma essential for invasion and egress. Elife 6:e27480

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dubey JP (2020) The history and life cycle of Toxoplasma gondii. In: Toxoplasma gondii, 3rd edn. Elsevier, pp 1–19

    Google Scholar 

  • Forman HJ, Zhang H (2021) Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. Nat Rev Drug Discov 20(9):689–709

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fulda S (2013) How to target apoptosis signaling pathways for the treatment of pediatric cancers. Front Oncol 3:22

    PubMed  PubMed Central  Google Scholar 

  • Gaji RY, Sharp AK, Brown AM (2021) Protein kinases in Toxoplasma gondii. Int J Parasitol 51(6):415–429

    Article  PubMed  CAS  Google Scholar 

  • Gibson LL, McKeever A, Coutinho E, Finke C, Pollak T (2020) Cognitive impact of neuronal antibodies: encephalitis and beyond. Transl Psychiatry 10(1):304

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Hamie M et al (2021) Imiquimod targets toxoplasmosis through modulating host toll-like receptor-MyD88 signaling. Front Immunol 12:629917

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed Central  CAS  Google Scholar 

  • 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

    PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • Holtz A, Basisty N, Schilling B (2021) Quantification and identification of post-translational modifications using modern proteomics approaches. Methods Mol Biol 2228:225–235

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Jo SH et al (2017) Calreticulin modulates the intracellular survival of mycobacteria by regulating ER-stress-mediated apoptosis. Oncotarget 8(35):58686–58698

    Article  PubMed  PubMed Central  Google Scholar 

  • Kannan G et al (2017) Pathogen-mediated NMDA receptor autoimmunity and cellular barrier dysfunction in schizophrenia. Transl Psychiatry 7(8):e1186–e1186

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • Khan A, Grigg ME (2017) Toxoplasma gondii: laboratory maintenance and growth. Curr Protoc Microbiol 44(1):20C:1.1-20C. 1.17

    Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kong L et al (2020) Tg ROP18 targets IL20RB for host-defense-related-STAT3 activation during Toxoplasma gondii infection. Parasit Vectors 13(1):400

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kravets E et al (2016) Guanylate binding proteins directly attack Toxoplasma gondii via supramolecular complexes. Elife 5:e11479

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed Central  CAS  Google Scholar 

  • Kumar A (2021a) Proteomics in host-protozoan parasite interactions and development of drug and vaccine. Adv Pharm Bull 11(2):209–211

    PubMed  Google Scholar 

  • Kumar V (2021b) Can proteomics-based approaches further help COVID-19 prevention and therapy? Expert Rev Proteomics 18(4):241–245

    Article  PubMed  CAS  Google Scholar 

  • Lang D et al (2018) Chronic Toxoplasma infection is associated with distinct alterations in the synaptic protein composition. J Neuroinflammation 15(1):216

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • Lathe R, Sapronova A, Kotelevtsev Y (2014) Atherosclerosis and Alzheimer-diseases with a common cause? Inflammation, oxysterols, vasculature. BMC Geriatr 14:36

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Li X et al (2022) Mitochondria shed their outer membrane in response to infection-induced stress. Science 375(6577):eabi4343

    Article  PubMed  CAS  Google Scholar 

  • Liu Q, Wang Z-D, Huang S-Y, Zhu X-Q (2015) Diagnosis of toxoplasmosis and typing of Toxoplasma gondii. Parasit Vectors 8:292

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed Central  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed Central  CAS  Google Scholar 

  • Mendez OA, Machado EF, Lu J, Koshy AA (2021) Injection with Toxoplasma gondii protein affects neuron health and survival. Elife 10:e67681

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • Nakazawa K, Sapkota K (2020) The origin of NMDA receptor hypofunction in schizophrenia. Pharmacol Ther 205:107426

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Nayeri T, Sarvi S, Sharif M, Daryani A (2021) Toxoplasma gondii: a possible etiologic agent for Alzheimer's disease. Heliyon 7(6):e07151

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Nissilä E et al (2018) Complement factor H and apolipoprotein E participate in regulation of inflammation in THP-1 macrophages. Front Immunol 9:2701

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Noguchi A et al (2021) Decreased lamin B1 levels affect gene positioning and expression in postmitotic neurons. Neurosci Res 173:22–33

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed Central  CAS  Google Scholar 

  • Park J, Hunter CA (2020) The role of macrophages in protective and pathological responses to Toxoplasma gondii. Parasite Immunol 42(7):e12712

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • Pascovici D et al (2019) Clinically relevant post-translational modification analyses-maturing workflows and bioinformatics tools. Int J Mol Sci 20(1):16

    Article  CAS  Google Scholar 

  • Pernas L et al (2014) Toxoplasma effector MAF1 mediates recruitment of host mitochondria and impacts the host response. PLoS Biol 12(4):e1001845

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Praefcke GJ (2018) Regulation of innate immune functions by guanylate-binding proteins. Int J Mol Sci 308(1):237–245

    CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Google Scholar 

  • Rahmatbakhsh M, Gagarinova A, Babu M (2021) Bioinformatic analysis of temporal and spatial proteome alternations during infections. Front Genet 12:667936

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Rashidi S et al (2021a) The host mTOR pathway and parasitic diseases pathogenesis. Parasitol Res 120(4):1151–1166

    Article  PubMed  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed Central  CAS  Google Scholar 

  • Sangaré LO et al (2019) Toxoplasma GRA15 activates the NF-κB pathway through interactions with TNF receptor-associated factors. MBio 10(4):e00808–e00819

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Selleck EM et al (2013) Guanylate-binding protein 1 (Gbp1) contributes to cell-autonomous immunity against Toxoplasma gondii. PLoS Pathog 9(4):e1003320

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Sidik SM et al (2016) A genome-wide CRISPR screen in Toxoplasma identifies essential apicomplexan genes. Cell 166(6):1423–1435. e12

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Stolf BS et al (2011) Protein disulfide isomerase and host-pathogen interaction. ScientificWorldJournal 11:1749–1761

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Sullivan WJ Jr, Jeffers V (2012) Mechanisms of Toxoplasma gondii persistence and latency. FEMS Microbiol Rev 36(3):717–733

    Article  PubMed  CAS  Google Scholar 

  • Sun H et al (2021) Comparative proteomics analysis for elucidating the interaction between host cells and Toxoplasma gondii. Front Cell Infect Microbiol 11:643001

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tomita T, Guevara RB, Shah LM, Afrifa AY, Weiss LM (2021) Secreted effectors modulating immune responses to Toxoplasma gondii. Life 11(9):988

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Witola WH et al (2014) ALOX12 in human toxoplasmosis. Infect Immun 82(7):2670–2679

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Xue J et al (2017) Thioredoxin reductase from Toxoplasma gondii: an essential virulence effector with antioxidant function. FASEB J 31(10):4447–4457

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Yao L et al (2021) Toxoplasma gondii Type-I ROP18 targeting human E3 ligase TRIM21 for immune escape. Front Cell Dev Biol 9:685913

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Zhou D et al (2011) Modulation of mouse macrophage proteome induced by Toxoplasma gondii tachyzoites in vivo. Parasitol Res 109(6):1637–1646

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

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.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Paul Nguewa or Raúl Manzano-Román.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Section Editor: Robin Flynn

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-022-07541-4

Keywords

Navigation