Assessment of Immune and Oxidative Stress Biomarkers in Toxoplasmosis Patients: A Comparative Study with Healthy Controls
Penilaian Biomarker Kekebalan Tubuh dan Stres Oksidatif pada Pasien Toksoplasmosis: Sebuah Studi Perbandingan dengan Kontrol yang Sehat
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(1) * Hamssa Majid Mustafa
Department of Medical Laboratory Techniques, Shatra Technical College, Southern Technical University, Shatra, Iraq
Iraq
(*) Corresponding Author
Abstract
Background; Toxoplasmosis, caused by the intracellular protozoan Toxoplasma gondii, is a widespread zoonotic infection that affects nearly one-third of the global population. While often asymptomatic in immunocompetent individuals, the disease can manifest severe complications in immunocompromised individuals, pregnant women, and neonates. Aims of the study; This study evaluates immune and oxidative stress biomarkers in toxoplasmosis patients to explore their role in disease severity and progression. Methodology; This study investigated biomarkers in 100 toxoplasmosis patients and 50 healthy controls, evenly divided by gender, from January 2023 to January 2024. Venous blood (5 mL) was collected, clotted, centrifuged, and serum stored at -20°C. Biomarkers measured included cytokines (IFN-γ, TNF-α, IL-10, CRP) and oxidative stress markers (MDA, SOD, CAT) using ELISA. Measurements followed manufacturer protocols, with absorbance readings taken via microplate reader. Statistical analysis assessed differences between patients and controls, with significance set at p<0.05. Results aimed to explore the role of immune and oxidative stress biomarkers in toxoplasmosis pathophysiology.Result; The study found no significant differences in demographic or lifestyle factors between Toxoplasma patients and controls, including age, gender distribution, residence, and smoking status. However, significant differences were observed in biomarker levels. Immune markers (IFN-γ, TNF-α, IL-10, and CRP) were elevated in patients compared to controls, indicating heightened immune activation. Oxidative stress markers showed contrasting trends: MDA levels were significantly higher in patients, reflecting increased lipid peroxidation, while antioxidant enzymes (SOD and CAT) were markedly lower, indicating reduced antioxidant defenses. These findings highlight the role of immune dysregulation and oxidative stress in Toxoplasma pathophysiology. Conclusions; This study highlights significant immune activation and oxidative stress in toxoplasmosis patients, with elevated inflammatory markers and reduced antioxidant enzymes. These biomarkers may serve as indicators of disease severity and progression.
Highlights:
- Toxoplasmosis affects one-third globally, severe in immunocompromised individuals.
- Analyzed immune, oxidative biomarkers in 100 patients vs. 50 controls.
- Elevated cytokines, oxidative stress markers; reduced antioxidant enzymes in patients..
Keywords: Toxoplasmosis, immune response, cytokines, oxidative stress, biomarkers, disease progression.
References
E. Ahmadpour et al., "Overview of Apoptosis, Autophagy, and Inflammatory Processes in *Toxoplasma gondii* Infected Cells," *Pathogens*, vol. 12, no. 2, p. 253, 2023. [Online]. Available: https://www.mdpi.com.
A. Babekir, S. Mostafa, and E. Obeng-Gyasi, "The Association of *Toxoplasma gondii* IgG and Cardiovascular Biomarkers," *International Journal of Environmental Research and Public Health*, vol. 18, no. 9, p. 4908, 2021.
J. Chen, W. Liao, and H. Peng, "*Toxoplasma gondii* Infection Possibly Reverses Host Immunosuppression to Restrain Tumor Growth," *Frontiers in Cellular and Infection Microbiology*, vol. 12, p. 959300, 2022. [Online]. Available: https://www.frontiersin.org.
R. S. Coombs, "Immediate IFN-γ Production Determines Host Compatibility Differences Between *Toxoplasma gondii* and *Neospora caninum* in Mice," unpublished, 2020. [Online]. Available: https://www.pitt.edu.
R. A. M. de Barros et al., "Toxoplasmosis in Humans and Animals Around the World: Diagnosis and Perspectives in the One Health Approach," *Acta Tropica*, vol. 231, p. 106432, 2022. [Online]. Available: https://www.html.
E. R. Teles, J. A. Portes, and W. de Souza, "New Morphological Observations on the Initial Events of *Toxoplasma gondii* Entry Into Host Cells," *Veterinary Parasitology*, vol. 322, p. 110006, 2023.
G. C. Dincel and H. T. Atmaca, "Role of Oxidative Stress in the Pathophysiology of *Toxoplasma gondii* Infection," *International Journal of Immunopathology and Pharmacology*, vol. 29, no. 2, pp. 226–240, 2016.
A. S. Doghish et al., "The Interplay Between Toxoplasmosis and Host miRNAs: Mechanisms and Consequences," *Pathology - Research and Practice*, vol. 250, p. 154790, 2023.
J. P. Dubey, *Toxoplasmosis of Animals and Humans*, 2nd ed., United States: CRC Press, 2016, pp. 19. [Online]. Available: https://doi.org/10.1201/9781420092370.
J. P. Dubey et al., "All About Toxoplasmosis in Cats: The Last Decade," *Veterinary Parasitology*, vol. 283, p. 109145, 2020. [Online]. Available: https://www.sciencedirect.com.
A. Ehrens, A. Hoerauf, and M. P. Hübner, "Eosinophils in Filarial Infections: Inducers of Protection or Pathology?," Frontiers in Immunology, vol. 13, 2022. [Online]. Available: https://www.frontiersin.org
P. J. Gaddi and G. S. Yap, "Cytokine Regulation of Immunopathology in Toxoplasmosis," Immunology and Cell Biology, vol. 85, no. 2, pp. 155–159, 2007.
R. T. Gazzinelli, A. Brezin, Q. Lian, R. B. Nussenblatt, and C. C. Chan, "Toxoplasma Gondii: Acquired Ocular Toxoplasmosis in the Murine Model, Protective Role of TNF-α and IFN-γ," Experimental Parasitology, vol. 78, no. 2, pp. 217–229, 1994.
B. Hajimohammadi et al., "A Meta-Analysis of the Prevalence of Toxoplasmosis in Livestock and Poultry Worldwide," EcoHealth, vol. 19, no. 1, pp. 55–74, 2022.
B. Henry, A. J. Phillips, L. D. Sibley, and A. Rosenberg, "A Combination of Four Toxoplasma Gondii Nuclear-Targeted Effectors Protects Against Interferon Gamma-Driven Human Host Cell Death," Mbio, vol. 15, no. 2, 2024. [Online]. Available: https://asm.org
M. M. Jafari et al., "Immune System Roles in Pathogenesis, Prognosis, Control, and Treatment of Toxoplasma Gondii Infection," International Immunopharmacology, vol. 124, p. 110872, 2023. [Online]. Available: https://www.sciencedirect.com
U. Karaman, T. Celik, T. R. Kiran, C. Colak, and N. U. Daldal, "Malondialdehyde, Glutathione, and Nitric Oxide Levels in Toxoplasma Gondii Seropositive Patients," The Korean Journal of Parasitology, vol. 46, no. 4, pp. 293–298, 2008.
B. Karkhanei, E. T. Ghane, and F. Mehri, "Evaluation of Oxidative Stress Level: Total Antioxidant Capacity, Total Oxidant Status and Glutathione Activity in Patients with COVID-19," New Microbes and New Infections, vol. 41, pp. 1–8, 2021.
L. Y. Kwok, D. Schlüter, C. Clayton, and D. Soldati, "The Antioxidant Systems in Toxoplasma Gondii and the Role of Cytosolic Catalase in Defence Against Oxidative Injury," Molecular Microbiology, vol. 51, no. 1, pp. 47–61, 2004.
J. Lekki-Jóźwiak and P. Bąska, "The Roles of Various Immune Cell Populations in Immune Response Against Helminths," International Journal of Molecular Sciences, vol. 24, no. 5, p. 2451, 2023. [Online]. Available: https://mdpi.com
Y. Liu et al., "Immunization with a DNA Vaccine Encoding Toxoplasma Gondii Superoxide Dismutase (TgSOD) Induces Partial Immune Protection Against Acute Toxoplasmosis in BALB/c Mice," BMC Infectious Diseases, vol. 17, pp. 1–8, 2017.
B. Maleki et al., "Toxoplasma Oocysts in the Soil of Public Places Worldwide: A Systematic Review and Meta-Analysis," Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 115, no. 5, pp. 471–481, 2021.
L. E. Mantilla-Muriel et al., "Serotyping, Host Genes and Cytokine Response in Human Ocular Toxoplasmosis," Microbial Pathogenesis, vol. 148, p. 104465, 2020. [Online]. Available: https://hal.science
A. A. Marchioro et al., "Analysis of Cytokines IFN-γ, TNF-α, TGF-β and Nitric Oxide in Amniotic Fluid and Serum of Pregnant Women with Toxoplasmosis in Southern Brazil," Cytokine, vol. 106, pp. 35–39, 2018.
C. F. Marcon, et al., "Macrophage Migration Inhibitory Factor (MIF) and Pregnancy May Impact the Balance of Intestinal Cytokines and the Development of Intestinal Pathology Caused by Toxoplasma Gondii Infection," Cytokine, vol. 136, 2020, Art. no. 155283. Available: https://www.sciencedirect.com.
I. Martinez-Espinosa, J. A. Serrato, and B. Ortiz-Quintero, "Role of IL-10-Producing Natural Killer Cells in the Regulatory Mechanisms of Inflammation During Systemic Infection," Biomolecules, vol. 11, 2021. Available: https://www.mdpi.com.
J. Matowicka-Karna, V. Dymicka-Piekarska, and H. Kemona, "Does Toxoplasma Gondii Infection Affect the Levels of IgE and Cytokines (IL-5, IL-6, IL-10, IL-12, and TNF-Alpha)?" Journal of Immunology Research, vol. 2009, Art. no. 374696, 2009.
S. K. Matta, et al., "Toxoplasma Gondii Infection and Its Implications Within the Central Nervous System," Nature Reviews Microbiology, vol. 19, no. 7, pp. 467-480, 2021.
C. S. Meira, et al., "Cerebral and Ocular Toxoplasmosis Related With IFN-γ, TNF-α, and IL-10 Levels," Frontiers in Microbiology, vol. 5, Art. no. 492, 2014.
C. S. Meira, et al., "Cerebral and Ocular Toxoplasmosis Related With IFN-γ, TNF-α, and IL-10 Levels," Frontiers in Microbiology, vol. 5, Art. no. 492, 2014.
S. Mese, T. Özekinci, and S. Atmaca, "Investigation of Correlation Between Toxoplasma Gondii IgG Positivity and Hs-CRP," Scandinavian Journal of Infectious Diseases, vol. 39, no. 10, p. 922, 2007.
E. Mitre and A. D. Klion, "Eosinophils and Helminth Infection: Protective or Pathogenic?," Seminars in Immunopathology, 2021.
R. Moghaddami, M. Mahdipour, and E. Ahmadpour, "Inflammatory Pathways of Toxoplasma Gondii Infection in Pregnancy," Travel Medicine and Infectious Disease, vol. 62, 2024, Art. no. 102760. Available: https://www.sciencedirect.com.
M. Montazeri, M. Sharif, S. Sarvi, S. Mehrzadi, E. Ahmadpour, and A. Daryani, "A Systematic Review of In Vitro and In Vivo Activities of Anti-Toxoplasma Drugs and Compounds (2006-2016)," Frontiers in Microbiology, vol. 8, Art. no. 25, 2017. Available: https://doi.org/10.3389/fmicb.2017.00025.
Z. H. A. Nazarlu, M. Matini, M. Bahmanzadeh, and F. Foroughi-Parvar, "Toxoplasma Gondii: A Possible Inducer of Oxidative Stress in Reproductive System of Male Rats," Iranian Journal of Parasitology, vol. 15, no. 4, pp. 521, 2020.
E. Ondari, et al., "Eosinophils and Bacteria: The Beginning of a Story," International Journal of Molecular Sciences, vol. 22, no. 15, Art. no. 8004, 2021. Available: https://www.mdpi.com.
M. Pal, et al., "Toxoplasmosis: An Emerging and Re-Emerging Zoonosis of Global Public Health Concern," American Journal of Infectious Disease and Microbiology, vol. 9, pp. 32-38, 2021. Available: https://www.academia.edu.
M. L. R. Paraboni, et al., "Comparative Study of Oxidative Stress and Antioxidative Markers in Patients Infected With Toxoplasma Gondii," Parasitology International, vol. 91, Art. no. 102645, 2022.
A. W. Pfaff, et al., "Cellular and Molecular Physiopathology of Congenital Toxoplasmosis: The Dual Role of IFN-γ," Parasitology, vol. 134, no. 13, pp. 1895-1902, 2007.
J. Pincemail, et al., "Oxidative Stress Status in COVID-19 Patients Hospitalized in Intensive Care Unit for Severe Pneumonia: A Pilot Study," Antioxidants, vol. 10, no. 2, Art. no. 257, 2021. Available: https://www.mdpi.com.
C. Pomares and J. G. Montoya, "Laboratory Diagnosis of Congenital Toxoplasmosis," Journal of Clinical Microbiology, vol. 54, no. 10, pp. 2448-2454, 2016. Available: https://doi.org/10.1128/JCM.00487-16.
A. Rostami, et al., "Global Prevalence of Latent Toxoplasmosis in Pregnant Women: A Systematic Review and Meta-Analysis," Clinical Microbiology and Infection, vol. 26, no. 6, pp. 673-683, 2020. Available: https://www.sciencedirect.com.
S. G. Sanchez and S. Besteiro, "The Pathogenicity and Virulence of Toxoplasma Gondii," Virulence, 2021. Available: https://www.tandfonline.com.
V. Sandri, et al., "Diagnostic Significance of C-Reactive Protein and Hematological Parameters in Acute Toxoplasmosis," Journal of Parasitic Diseases, vol. 44, pp. 785-793, 2020.
A. Shrivastava, et al., "An Assessment of Serum Oxidative Stress and Antioxidant Parameters in Patients Undergoing Treatment for Cervical Cancer," Free Radical Biology and Medicine, vol. 167, pp. 29-35, 2021.
L. D. Sibley, R. Lawson, and E. Weidner, "Superoxide Dismutase and Catalase in Toxoplasma Gondii," Molecular and Biochemical Parasitology, vol. 19, no. 1, pp. 83-87, 1986.
L. D. Sibley, R. Lawson, and E. Weidner, "Superoxide Dismutase and Catalase in Toxoplasma Gondii," Molecular and Biochemical Parasitology, vol. 19, no. 1, pp. 83-87, 1986.
J. Skutnik-Radziszewska, et al., "Salivary Antioxidants and Oxidative Stress in Psoriatic Patients: Can Salivary Total Oxidant Status and Oxidative Status Index Be a Plaque Psoriasis Biomarker?" Oxidative Medicine and Cellular Longevity, vol. 2020, Art. no. 9086024, 2020. Available: https://www.wiley.com.
I. Tartarelli, et al., "During Host Cell Traversal and Cell-to-Cell Passage, Toxoplasma Gondii Sporozoites Inhabit the Parasitophorous Vacuole and Posteriorly Release Dense Granule Protein-Associated Membranous Trails," International Journal for Parasitology, vol. 50, no. 13, pp. 1099-1115, 2020.
E. H. Wilson, U. Wille-Reece, F. Dzierszinski, and C. A. Hunter, "A Critical Role for IL-10 in Limiting Inflammation During Toxoplasmic Encephalitis," Journal of Neuroimmunology, vol. 165, no. 1-2, pp. 63-74, 2005.
S. Yazar, E. Kilic, R. Saraymen, and I. Sahin, "Serum Malondialdehyde Levels in Toxoplasma Seropositive Patients," Annals of Saudi Medicine, vol. 23, no. 6, pp. 413-415, 2003.
X. Y. Zhao and S. E. Ewald, "The Molecular Biology and Immune Control of Chronic Toxoplasma Gondii Infection," The Journal of Clinical Investigation, 2020. Available: https://www.jci.org.
J. Zińczuk, et al., "Pro-Oxidant Enzymes, Redox Balance and Oxidative Damage to Proteins, Lipids and DNA in Colorectal Cancer Tissue: Is Oxidative Stress Dependent on Tumor Budding and Inflammatory Infiltration?" Cancers, vol. 12, no. 6, Art. no. 1636, 2020. Available: https://www.mdpi.com.
H. M. Mustafa, A. A. Hamad, and O. A. Mohsein, "Entamoeba Histolytica and Giardia Lamblia Predominance in Iraq’s Southern Governorates," International Journal of Environmental Health Engineering, vol. 13, no. 1, pp. 10, Apr. 2024. Available: https://doi.org/10.4103/ijehe.ijehe_60_23.
H. M. Mustafa, A. A. Hamad, and O. A. Mohsein, "Detection of the Levels of Immune Cytokines (IL-4, IL-5, TNF-α) in School-Age and Preschoolers With an Ascaris Lumbricoides Infection," Journal of Parasitic Diseases, vol. 48, pp. 782-787, 2024. Available: https://doi.org/10.1007/s12639-024-01715-w.
H. M. Mustafa, A. A. Hamad, and O. A. Mohsein, "Investigating Specific Calprotectin and Immunological Markers Associated With Intestinal Infections Caused by Entamoeba Histolytica," Iranian Journal of Veterinary Medicine, vol. 18, no. 4, pp. 535-544, 2024. Available: https://doi.org/10.32598/ijvm.18.4.1005546.
