Association of Some Pro-and Anti-Inflammatory Cytokines Response Pattern against Toxoplasmosis in Newly Married Couples
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Abstract
Background: The study aimed to investigate the association between cytokine profiles and toxoplasmosis in newly married couples, with identifying the immunological markers to minimizing fertility complications through early detection and intervention.
Methods: From May 2024 to February 2025, blood samples of 480 newlywed couples in Zakho City, Iraq, were evaluated for Anti-Toxoplasma G (IgG) and M (IgM) antibodies, as well as serum cytokines like Interleukin 12 (IL-12), Tumer Necrosis Factor α (TNF-α), Interleukin10 (IL-10), and Transforming Growth Factor ß1 (TGFß1), using ELISA. Additionally, C Reactive protein (CRP) and Erythrocyte Sedimentation Rate (ESR) were also estimated.
Results: The overall seroprevalence of Anti-Toxoplasma antibodies were 25.8% (124/480), constituting 18.2% (88/480) for IgG, and 7.5% (36/480) for IgM, with highly significant difference (P< 0.001). Rates were higher in males, with age-related differences observed for both IgG and IgM. While statistically significant differences were reported for IgM alone relates to gender. Regarding cytokines, seropositive individuals showed significantly higher IL-10 and IL-12 levels than controls: IL-10 (IgG: 85.88±9.67 vs 37.88±5.06; IgM: 80.95±13.19 vs 51.72±6.19 pg/mL) and IL-12 (IgG: 22.43±3.05 vs 10.08±1.03; IgM: 29.25±5.46 vs 11.83±1.06 pg/mL). Besides, TNF-α elevated in the IgM group only.
Conclusion: Elevated IL-10 and IL-12 levels in seropositive individuals suggest active immune modulation, while TNF-α dynamics point to stage-specific responses, higher in acute (IgM) infections. These immune patterns may influence reproductive health, underscoring the importance of early diagnosis and immune monitoring to reduce potential fertility complications, particularly in early marriage.
1. Yang N, Li M, Yang H, et al. Transcriptional profiles analysis of effects of Toxoplasma gondii rhoptry protein 16 on THP-1 macrophages. Front Cell Infect Microbial. 2025;14:1436712.
2. Asfaram S, Zarei Z, Teimoorpour R, et al. Serological Evaluation and Molecular Genotyping of Toxoplasma gondii in Pregnant Women in Meshkin-Shahr District, Northwestern. Iran J Parasitol. 2025; 20(1):44-53.
3. Barratt JL, Harkness J, Marriott D, et al. Importance of nonenteric protozoan infections in immunocompromised people. Clin Microbiol Rev. 2010; 23(4):795-836.
4. Robert-Gangneux F, Dardé ML. Epidemiology of and diagnostic strategies for toxoplasmosis. Clin Microbiol Rev. 2012; 25(2):264-96.
5. Machala L, Kodym P, Malý M, et al. [Toxoplasmosis in immunocompromised patients]. Epidemiol Mikrobiol Imunol. 2015; 64(2):59-65.
6. Salih JM, Mero WM, Eassa SH. Seroprevalence and some demographic factors associated with Toxoplasma gondii infection among female population in Duhok province, Iraq. Int J Res Med Sci. 2020; 8(3):921.
7. Flegr J, Prandota J, Sovičková M, et al. Toxoplasmosis–a global threat. Correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries. PLoS ONE. 2014; 9(3): e90203.
8. Abdulla HE, Abood AS, Kadhim HS, et al. The impact of toxoplasmosis on Seminal fluid analysis in association with infertility. Inter J of Scientific & Engin Research. 2016; 7(5):70-3.
9. Dalimi A, Abdoli A. Toxoplasma gondii and male reproduction impairment: a new aspect of toxoplasmosis research. Jundishapur J Microbiol. 2013; 6(8):e7184.
10. Zheng YX, Zhang XX, Hernandez JA, et al. Transcriptomic analysis of reproductive damage in the epididymis of male Kunming mice induced by chronic infection of Toxoplasma gondii PRU strain. Parasit Vectors. 2019; 12(1):529.
11. Saud MJ, Abd M, Adnan A, et al. Implications of Toxoplasma Infection on Women’s Immune Status in Baghdad Province. Journal Of Communicable Diseases. 2023; 55:62-66.
12. Al-Malki ES. Toxoplasmosis: stages of the protozoan life cycle and risk assessment in humans and animals for an enhanced awareness and an improved socio-economic status. Saudi z Biol Sci. 2021; 28(1):962-969.
13. Petríková J. Toxoplasma and Autoimmunity. Inf. & Autoimmun. 2024 3rd ed.2024; 657-674 Academic Press.
14. Sana M, Rashid M, Rashid I, et al. Immune response against toxoplasmosis—some recent updates RH: Toxoplasma gondii immune response. Int J Immunopathol Pharmacol. 2022; 36:03946320221078436.
15. Mizuri SS, Ramadhan CA, Mero WM. Associations between toxoplasmosis and rheumatoid arthritis among patients in Zakho City, Kurdistan Region/Iraq. Zanco J Med Sci. 2024; 28(3):518-25.
16. Araujo WM, Ayo CM, Previato M, et al. Role of interleukin 1β and interleukin 10 variants on ocular toxoplasmosis in Brazilian individuals. Front Ophthalmol (Lausanne). 2023; 3:1183167.
17. Li XL, Wei HX, Zhang H, et al. A meta-analysis on risks of adverse pregnancy outcomes in Toxoplasma gondii infection. PloS One. 2014; 9(5): e97775.
18. Moghaddami R, Mahdipour M, Ahmadpour E. Inflammatory pathways of Toxoplasma gondii infection in pregnancy. Travel Med Infect Dis. 2024; 62:102760.
19. Mustafa KM, Mohammed AB, Mero WM, et al . Seroprevalence of Toxoplasma gondii antibodies and associated risk factors among women in Zakho City, Iraq. Cureus. 2024;16(3). e56328.
20. Chan BT, Amal RN, Noor Hayati et al. Seroprevalence of toxoplasmosis among migrant workers from different Asian countries working in Malaysia. Southeast Asian J Trop Med Public Health. 2008; 39(1):9-13.
21. Mustafa KM, Mero WM, Mohammed AB. The seroprevalence of Toxoplasma gondii infection among male population in Zakho City, Duhok Province, J Adv Zool. 2023; 44:301-306.
22. Al-Atroshi AMA, Mero WM. Seroprevalence of Anti-Toxoplasma antibodies among women of childbearing age in Duhok Province. Journal of University of Zakho (JUOZ). 2013; 1(1):44-49.
23. Sulaiman AA. Seroprevalence of anti-Toxoplasma antibodies among couple referred to a pre-marriage screening center in Duhok province, Iraq. The Journal of The University of Duhok. 2023; 26(2): 52-60.
24. El-Henawy AA, Hafez EAR, Nabih N, et al. Anti-Toxoplasma antibodies in Egyptian rheumatoid arthritis patients. Rheumatol Int. 2017; 37(5): 785-790.
25. Salman YJ, Mohammed KA. Relationship between Toxoplasma gondii and arthritis among patients in Kirkuk City. Int J Curr Res Aca Rev. 2015; 3(8):175–187.
26. Sandri V, Gonçalves IL, Machado das Neves G, et al. Diagnostic significance of C-reactive protein and hematological parameters in acute toxoplasmosis. J Parasit Dis. 2020; 44(4): 785-793.
27. Kadhum LS, Aakool AA, Kadhim AJ. Toxoplasma gondii Infection Related and Interleukin 10 In Wasit Province Patients. J Surv Fish. 2023; 10: 2157-2163.
28. Masoori L, Rezaei N, Molazadeh M, et al. Development of rheumatoid arthritis by toxoplasmosis in Iranian patients. J Kerman Univ Med Sci. 2021; 28(4):412-419.
29. Siemons L, Ten Klooster PM, Vonkeman HE, et al. How age and sex affect the erythrocyte sedimentation rate and C-reactive protein in early rheumatoid arthritis. BMC Musculoskelet Disord. 2014; 6;15(1):368.
30. Quiros-Roldan E, Sottini A, Natali PG, et al. The impact of immune system aging on infectious diseases. Microorganisms. 2024; 12(4):775.
31. Matowicka KJ, Dymicka PV, Kemona H. Does Toxoplasma gondii infection affect the levels of IgE and cytokines (IL‐5, IL‐6, IL‐10, IL‐12, and TNF‐alpha)? Clin Dev Immunol. 2009; 2009:374696.
32. Young JC, Broncel M, Teague H, et al. Phosphorylation of Toxoplasma gondii secreted proteins during acute and chronic stages of infection. mSphere. 2020; 5(5):e00792-20.
33. Babaie J, Samira A, Robab H, et al. 'Immunization of C57BL/6 mice with GRA2 combined with MPL conferred partial immune protection against Toxoplasma gondii . IBJ. 2018; 22(1): 22-32.
34. Marchioro AA, Colli CM, de Souza CZ, 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. 2018; 106: 35–39.
35. Bakr HM. Role of Toxoplasma surface proteins in host-parasite immune modulation. Cell Mol Biol (Noisy-le-grand). 2025; 71(3): 146-150.
36. Gazzinelli RT, Wysocka M, Hayashi S, et al. Parasite-induced IL-12 stimulates early IFN-gamma synthesis and resistance during acute infection with Toxoplasma gondii . J Immunol. 1994; 153(6):2533-43.
37. Alsailawi HA, Ayat SS, Mudhafar et al. Immunohistochemical study of TGF-β, PDL-1, and IL-10 in patients with Toxoplasma gondii . Na J Adv Res Rev. 2022; 14(1): 436-48.
38. Zare-Bidaki M, Assar S, Hakimi H, et al. TGF-β in Toxoplasmosis: Friend or foe? Cytokine. 2016; 86: 29-35.
39. Kanash AK, Yousif JJ. The Association of Toxoplasmosis and the Levels of IL-10 and IL-12 in Women with Breast Cancer. Int J Drug Deliv Technol. 2021; 11(2): 265-268.
40. Gómez-Chávez F, Cañedo-Solares I, Ortiz-Alegría LB, et al. A proinflammatory immune response might determine Toxoplasma gondii vertical transmission and severity of clinical features in congenitally infected newborns. Front Immunol. 2020; 11:390.
41. Kuba RH, Zghair KH, Alosami MH. Detection of Toxoplasma antibodies and TNF-α in rheumatoid arthritis patients treated with methotrexate. Iraqi Journal of Science. 2014; 55: 1535-1540.
42. Denis J, Gommenginger C, Strechie T, et al. Dynamic immune profile in French toxoplasmosis patients. J Infect Dis. 2022; 226(10): 1834-1841.
43. Meira CS, Pereira-Chioccola VL, Vidal JE, et al. Cerebral and ocular toxoplasmosis related with IFN-γ, TNF-α, and IL-10 levels. Front Microbiol. 2014; 5:492.
44. Khan IA, Moretto M. Immune responses to Toxoplasma gondii . Curr Opin Immunol. 2022; 77: 102226.
2. Asfaram S, Zarei Z, Teimoorpour R, et al. Serological Evaluation and Molecular Genotyping of Toxoplasma gondii in Pregnant Women in Meshkin-Shahr District, Northwestern. Iran J Parasitol. 2025; 20(1):44-53.
3. Barratt JL, Harkness J, Marriott D, et al. Importance of nonenteric protozoan infections in immunocompromised people. Clin Microbiol Rev. 2010; 23(4):795-836.
4. Robert-Gangneux F, Dardé ML. Epidemiology of and diagnostic strategies for toxoplasmosis. Clin Microbiol Rev. 2012; 25(2):264-96.
5. Machala L, Kodym P, Malý M, et al. [Toxoplasmosis in immunocompromised patients]. Epidemiol Mikrobiol Imunol. 2015; 64(2):59-65.
6. Salih JM, Mero WM, Eassa SH. Seroprevalence and some demographic factors associated with Toxoplasma gondii infection among female population in Duhok province, Iraq. Int J Res Med Sci. 2020; 8(3):921.
7. Flegr J, Prandota J, Sovičková M, et al. Toxoplasmosis–a global threat. Correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries. PLoS ONE. 2014; 9(3): e90203.
8. Abdulla HE, Abood AS, Kadhim HS, et al. The impact of toxoplasmosis on Seminal fluid analysis in association with infertility. Inter J of Scientific & Engin Research. 2016; 7(5):70-3.
9. Dalimi A, Abdoli A. Toxoplasma gondii and male reproduction impairment: a new aspect of toxoplasmosis research. Jundishapur J Microbiol. 2013; 6(8):e7184.
10. Zheng YX, Zhang XX, Hernandez JA, et al. Transcriptomic analysis of reproductive damage in the epididymis of male Kunming mice induced by chronic infection of Toxoplasma gondii PRU strain. Parasit Vectors. 2019; 12(1):529.
11. Saud MJ, Abd M, Adnan A, et al. Implications of Toxoplasma Infection on Women’s Immune Status in Baghdad Province. Journal Of Communicable Diseases. 2023; 55:62-66.
12. Al-Malki ES. Toxoplasmosis: stages of the protozoan life cycle and risk assessment in humans and animals for an enhanced awareness and an improved socio-economic status. Saudi z Biol Sci. 2021; 28(1):962-969.
13. Petríková J. Toxoplasma and Autoimmunity. Inf. & Autoimmun. 2024 3rd ed.2024; 657-674 Academic Press.
14. Sana M, Rashid M, Rashid I, et al. Immune response against toxoplasmosis—some recent updates RH: Toxoplasma gondii immune response. Int J Immunopathol Pharmacol. 2022; 36:03946320221078436.
15. Mizuri SS, Ramadhan CA, Mero WM. Associations between toxoplasmosis and rheumatoid arthritis among patients in Zakho City, Kurdistan Region/Iraq. Zanco J Med Sci. 2024; 28(3):518-25.
16. Araujo WM, Ayo CM, Previato M, et al. Role of interleukin 1β and interleukin 10 variants on ocular toxoplasmosis in Brazilian individuals. Front Ophthalmol (Lausanne). 2023; 3:1183167.
17. Li XL, Wei HX, Zhang H, et al. A meta-analysis on risks of adverse pregnancy outcomes in Toxoplasma gondii infection. PloS One. 2014; 9(5): e97775.
18. Moghaddami R, Mahdipour M, Ahmadpour E. Inflammatory pathways of Toxoplasma gondii infection in pregnancy. Travel Med Infect Dis. 2024; 62:102760.
19. Mustafa KM, Mohammed AB, Mero WM, et al . Seroprevalence of Toxoplasma gondii antibodies and associated risk factors among women in Zakho City, Iraq. Cureus. 2024;16(3). e56328.
20. Chan BT, Amal RN, Noor Hayati et al. Seroprevalence of toxoplasmosis among migrant workers from different Asian countries working in Malaysia. Southeast Asian J Trop Med Public Health. 2008; 39(1):9-13.
21. Mustafa KM, Mero WM, Mohammed AB. The seroprevalence of Toxoplasma gondii infection among male population in Zakho City, Duhok Province, J Adv Zool. 2023; 44:301-306.
22. Al-Atroshi AMA, Mero WM. Seroprevalence of Anti-Toxoplasma antibodies among women of childbearing age in Duhok Province. Journal of University of Zakho (JUOZ). 2013; 1(1):44-49.
23. Sulaiman AA. Seroprevalence of anti-Toxoplasma antibodies among couple referred to a pre-marriage screening center in Duhok province, Iraq. The Journal of The University of Duhok. 2023; 26(2): 52-60.
24. El-Henawy AA, Hafez EAR, Nabih N, et al. Anti-Toxoplasma antibodies in Egyptian rheumatoid arthritis patients. Rheumatol Int. 2017; 37(5): 785-790.
25. Salman YJ, Mohammed KA. Relationship between Toxoplasma gondii and arthritis among patients in Kirkuk City. Int J Curr Res Aca Rev. 2015; 3(8):175–187.
26. Sandri V, Gonçalves IL, Machado das Neves G, et al. Diagnostic significance of C-reactive protein and hematological parameters in acute toxoplasmosis. J Parasit Dis. 2020; 44(4): 785-793.
27. Kadhum LS, Aakool AA, Kadhim AJ. Toxoplasma gondii Infection Related and Interleukin 10 In Wasit Province Patients. J Surv Fish. 2023; 10: 2157-2163.
28. Masoori L, Rezaei N, Molazadeh M, et al. Development of rheumatoid arthritis by toxoplasmosis in Iranian patients. J Kerman Univ Med Sci. 2021; 28(4):412-419.
29. Siemons L, Ten Klooster PM, Vonkeman HE, et al. How age and sex affect the erythrocyte sedimentation rate and C-reactive protein in early rheumatoid arthritis. BMC Musculoskelet Disord. 2014; 6;15(1):368.
30. Quiros-Roldan E, Sottini A, Natali PG, et al. The impact of immune system aging on infectious diseases. Microorganisms. 2024; 12(4):775.
31. Matowicka KJ, Dymicka PV, Kemona H. Does Toxoplasma gondii infection affect the levels of IgE and cytokines (IL‐5, IL‐6, IL‐10, IL‐12, and TNF‐alpha)? Clin Dev Immunol. 2009; 2009:374696.
32. Young JC, Broncel M, Teague H, et al. Phosphorylation of Toxoplasma gondii secreted proteins during acute and chronic stages of infection. mSphere. 2020; 5(5):e00792-20.
33. Babaie J, Samira A, Robab H, et al. 'Immunization of C57BL/6 mice with GRA2 combined with MPL conferred partial immune protection against Toxoplasma gondii . IBJ. 2018; 22(1): 22-32.
34. Marchioro AA, Colli CM, de Souza CZ, 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. 2018; 106: 35–39.
35. Bakr HM. Role of Toxoplasma surface proteins in host-parasite immune modulation. Cell Mol Biol (Noisy-le-grand). 2025; 71(3): 146-150.
36. Gazzinelli RT, Wysocka M, Hayashi S, et al. Parasite-induced IL-12 stimulates early IFN-gamma synthesis and resistance during acute infection with Toxoplasma gondii . J Immunol. 1994; 153(6):2533-43.
37. Alsailawi HA, Ayat SS, Mudhafar et al. Immunohistochemical study of TGF-β, PDL-1, and IL-10 in patients with Toxoplasma gondii . Na J Adv Res Rev. 2022; 14(1): 436-48.
38. Zare-Bidaki M, Assar S, Hakimi H, et al. TGF-β in Toxoplasmosis: Friend or foe? Cytokine. 2016; 86: 29-35.
39. Kanash AK, Yousif JJ. The Association of Toxoplasmosis and the Levels of IL-10 and IL-12 in Women with Breast Cancer. Int J Drug Deliv Technol. 2021; 11(2): 265-268.
40. Gómez-Chávez F, Cañedo-Solares I, Ortiz-Alegría LB, et al. A proinflammatory immune response might determine Toxoplasma gondii vertical transmission and severity of clinical features in congenitally infected newborns. Front Immunol. 2020; 11:390.
41. Kuba RH, Zghair KH, Alosami MH. Detection of Toxoplasma antibodies and TNF-α in rheumatoid arthritis patients treated with methotrexate. Iraqi Journal of Science. 2014; 55: 1535-1540.
42. Denis J, Gommenginger C, Strechie T, et al. Dynamic immune profile in French toxoplasmosis patients. J Infect Dis. 2022; 226(10): 1834-1841.
43. Meira CS, Pereira-Chioccola VL, Vidal JE, et al. Cerebral and ocular toxoplasmosis related with IFN-γ, TNF-α, and IL-10 levels. Front Microbiol. 2014; 5:492.
44. Khan IA, Moretto M. Immune responses to Toxoplasma gondii . Curr Opin Immunol. 2022; 77: 102226.
| Files | ||
| Issue | Vol 20 No 4 (2025) | |
| Section | Original Article(s) | |
| Keywords | ||
| Toxoplasmosis Interleukin-12 Tumor necrosis factor-alpha Interleukin-10 Transforming growth factor-beta1 | ||
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How to Cite
1.
Muhamad Mizuri SS, Salih Mero WM, Mohammed Khalid H. Association of Some Pro-and Anti-Inflammatory Cytokines Response Pattern against Toxoplasmosis in Newly Married Couples. Iran J Parasitol. 2025;20(4):500-509.
