The Protective Role of IL-17 Against Parasitic Infections: A Meta-Analysis Study
Abstract
Background: Interleukin-17 (IL-17) has been implicated in protective immune responses against various parasitic infections. Understanding its role may clarify host defense mechanisms and potential therapeutic applications. Aims: This systematic review and meta-analysis aimed to synthesize evidence regarding IL-17 expression, concentration, and functional activity in parasitic diseases. Materials and Methods: Following PRISMA recommendations, an extensive search of major scientific databases was conducted (including PubMed, Scopus, Web of Science, and Embase). Twenty-one articles involving both human participants and animal models were included if they evaluated IL-17 in the context of parasitic infection. Data were analyzed for pooled mean differences, correlations, heterogeneity, and publication bias. Results: Protective immune responses against Toxoplasma gondii, Leishmania spp., Giardia lamblia, Entamoeba histolytica, Schistosoma mansoni, and other parasites were consistently associated with IL-17 activity. The pooled analysis demonstrated a statistically significant mean difference (MD = 1.45, 95% CI: 0.92–1.98, p = 0.002), indicating that elevated IL-17 levels correlated with improved outcomes, including decreased parasitic load and reduced disease severity. Linear regression revealed a significant positive correlation between IL-17 concentrations and host protection (R² = 0.58, p = 0.012). Moderate heterogeneity was observed (I² = 68%), but Egger’s test suggested no major publication bias. Conclusion: This study strengthens the understanding of IL-17 as a pivotal immunological indicator in parasitic diseases. Elevated IL-17 levels are associated with host protection and may represent a promising therapeutic target to enhance resistance against parasitic infections.
Keywords:
Meta-Analysis, IL-17, Parasitic Infections, Pro-Inflammatory
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References
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Drinkall, E., Wass, M. J., Coffey, T. J., & Flynn, R. J. (2017). A rapid IL-17 response to Cryptosporidium parvum in the bovine intestine. Veterinary Immunology and Immunopathology, 191, 1–4. https://doi.org/10.1016/j.vetimm.2017.07.009
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Guedes, P. M. D. M., Gutierrez, F. R., Maia, F. L., Milanezi, C. M., Silva, G. K., Pavanelli, W. R., & Silva, J. S. (2010). IL-17 produced during Trypanosoma cruzi infection plays a central role in regulating parasite-induced myocarditis. PloS Neglected Tropical Diseases, 4(2), e604.https://doi.org/10.1371/journal.pntd.0000604
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Labsi, M., Soufli, I., Khelifi, L., Amir, Z. C., & Touil-Boukoffa, C. (2018). In vivo treatment with IL-17A attenuates hydatid cyst growth and liver fibrogenesis in an experimental model of echinococcosis. Acta Tropica, 181, 6-10. https://doi.org/10.1016/j.actatropica.2018.01.014
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Mills, K. H. (2023). IL-17 and IL-17-producing cells in protection versus pathology. Nature Reviews Immunology, 23(1), 38-54. https://doi.org/10.1038/s41577-022-00746-9
Mohammed, H. S., Ali., S. A. K., Mohammed, L. O., & Mohammed, M. S. (2022). Prevalence of amoebiasis and estimation of certain cytokines (IL-17, IFN- γ and TNF- α) in children with amoebic infection in Sulaimani Province / Iraq. Iraq Medical Journal, 6(1), 6–15. https://doi.org/10.22317/imj.v6i1.1148
Moroda, M., Takamoto, M., Iwakura, Y., Nakayama, J., & Aosai, F. (2017). Interleukin-17A-deficient mice are highly susceptible to Toxoplasma gondii infection due to excessively induced T. gondii HSP70 and interferon gamma production. Infection and Immunity, 85(12), 10-1128. https://doi.org/10.1128/iai.00399-17
Paerewijck, O., Maertens, B., Dreesen, L., Van Meulder, F., Peelaers, I., Ratman, D., ... & Geldhof, P. (2017). Interleukin-17 receptor A (IL-17RA) as a central regulator of the protective immune response against Giardia. Scientific Reports, 7(1), 8520. https://doi.org/10.1038/s41598-017-08590-x
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Singer, S. M. (2016). Control of giardiasis by interleukin-17 in humans and mice—are the questions all answered?. Clinical and Vaccine Immunology, 23(1), 2-5. https://doi.org/10.1128/CVI.00648-15
Singh, T. P., Carvalho, A. M., Sacramento, L. A., Grice, E. A., & Scott, P. (2021). Microbiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis. PLoS Pathogens, 17(10), e1009693.https://doi.org/10.1371/journal.ppat.1009693
Terrazas, C., Varikuti, S., Kimble, J., Moretti, E., Boyaka, P. N., & Satoskar, A. R. (2015). IL-17A promotes susceptibility during experimental visceral leishmaniasis caused by Leishmania donovani. The FASEB Journal, 30(3), 1135–1143. https://doi.org/10.1096/fj.15-277202
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Abdul-Aziz, A. I. (2025). Molecular study and determining the levels of some interleukins in children with Entamoeba histolytica. Cytokine, 188, 156890. https://doi.org/10.1016/j.cyto.2025.156890
Alhussine, M. G., Hasan, S. A., Al-Hussainy, S. A. G., Al-Fahham, A. A. (2025). Evaluation of serum interleukin-17 in women with vaginitis. International Journal of Medical Science and Dental Health, 11(6), 7–13. https://doi.org/10.55640/ijmsdh-11-06-02
Al-Masoudi, H. K., Al-Hamadani, K. C., & Khiarull, I. A. (2021). Interleukin 17 cytokine profiles in patients with cystic echinococcosis in Babylon province, Iraq. Archives of Razi Institute, 76(5), 1493- 1500. https://doi.org/10.22092/ari.2021.355855.1730
Anuradha, R., Munisankar, S., Bhootra, Y., Jagannathan, J., Dolla, C., Kumaran, P., ... & Babu, S. (2016). Systemic cytokine profiles in Strongyloides stercoralis infection and alterations following treatment. Infection and Immunity, 84(2), 425-431. https://doi.org/10.1128/iai.01354-15
Babaloo, Z., Oskoei, M. R., Kohansal, M. H., Barac, A., & Ahmadpour, E. (2020). Serum profile of IL-1β and IL-17 cytokines in patients with visceral leishmaniasis. Comparative Immunology, Microbiology and Infectious Diseases, 69, 101431. https://doi.org/10.1016/j.cimid.2020.101431
Barreto, A. V., Lacerda, G. A., Figueiredo, A. L., Diniz, G. T., Gomes, E. C., Domingues, A. L., Barbosa, C. S., Montengro, S. M., & Morais, C. N. (2016). Evaluation of serum levels of IL-9 and IL-17 in human Schistosoma mansoni infection and their relationship with periportal fibrosis. Immunobiology, 221(12), 1351–1354. https://doi.org/10.1016/j.imbio.2016.07.014
Beringer, A., Noack, M., & Miossec, P. (2016). IL-17 in chronic inflammation: from discovery to targeting. Trends in Molecular Medicine, 22(3), 230-241. https://doi.org/10.1016/j.molmed.2016.01.001
Chen, F., Wu, W., Millman, A., Craft, J. F., Chen, E., Patel, N... & Gause, W. (2019). Neutrophils prime a long-lived effector macrophage phenotype that mediates accelerated helminth expulsion. Nature Immunology, 15, 938–946. https://doi.org/10.1038/ni.2984
Dabirzadeh, M., Ghoryani, M., Poursamimi, J., & Fouladi, B. (2024). Association of toxoplasmosis with serum TGF-β, IL-17, and IL-6 levels in individuals with diabetes. Iranian Journal of Allergy, Asthma and Immunology, 23(6), 753-758. https://doi.org/10.18502/ijaai.v23i6.17384
Dann, S. M., Manthey, C. F., Le, C., Miyamoto, Y., Gima, L., Abrahim, A., ... & Eckmann, L. (2015). IL-17A promotes protective IgA responses and expression of other potential effectors against the lumen-dwelling enteric parasite Giardia. Experimental Parasitology, 156, 68-78. https://doi.org/10.1016/j.exppara.2015.06.003
Dietze-Schwonberg, K., Lopez Kostka, S., Lorenz, B., Regen, T., Waisman, A., von Stebut, E. (2019). IL-17A/F in Leishmania major-resistant C57BL/6 mice. Experimental Dermatology, 28(3), 321–323. https://doi.org/10.1111/exd.13896
Drinkall, E., Wass, M. J., Coffey, T. J., & Flynn, R. J. (2017). A rapid IL-17 response to Cryptosporidium parvum in the bovine intestine. Veterinary Immunology and Immunopathology, 191, 1–4. https://doi.org/10.1016/j.vetimm.2017.07.009
Gaffen, S. L. (2009). Structure and signalling in the IL-17 receptor family. Nature Reviews Immunology, 9(8), 556-567. https://doi.org/10.1038/nri2586
Guedes, P. M. D. M., Gutierrez, F. R., Maia, F. L., Milanezi, C. M., Silva, G. K., Pavanelli, W. R., & Silva, J. S. (2010). IL-17 produced during Trypanosoma cruzi infection plays a central role in regulating parasite-induced myocarditis. PloS Neglected Tropical Diseases, 4(2), e604.https://doi.org/10.1371/journal.pntd.0000604
Hadi, H. S., Shubar, S. N. A., Jaffar, A. M., Al-Fahham, A. A. (2024). Structure and physiological significance of IL-17: A review article. International Journal of Health & Medical Research, 3(9), 666–669. https://doi.org/10.58806/ijhmr.2024.v3i09n03
Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009). IL-17 and Th17 cells in immune regulation and host defence. Annual Review of Immunology, 27, 485–517. https://doi.org/10.1146/annurev.immunol.021908.132710
Labsi, M., Soufli, I., Khelifi, L., Amir, Z. C., & Touil-Boukoffa, C. (2018). In vivo treatment with IL-17A attenuates hydatid cyst growth and liver fibrogenesis in an experimental model of echinococcosis. Acta Tropica, 181, 6-10. https://doi.org/10.1016/j.actatropica.2018.01.014
Lechner, C. J., Grüner, B., Huang, X., Hoffmann, W. H., Kern, P., & Soboslay, P. T. (2012). Parasite‐specific IL‐17‐type cytokine responses and soluble IL‐17 receptor levels in Alveolar Echinococcosis patients. Journal of Immunology Research, 2012(1), 735342. https://doi.org/10.1155/2012/735342
Mills, K. H. (2023). IL-17 and IL-17-producing cells in protection versus pathology. Nature Reviews Immunology, 23(1), 38-54. https://doi.org/10.1038/s41577-022-00746-9
Mohammed, H. S., Ali., S. A. K., Mohammed, L. O., & Mohammed, M. S. (2022). Prevalence of amoebiasis and estimation of certain cytokines (IL-17, IFN- γ and TNF- α) in children with amoebic infection in Sulaimani Province / Iraq. Iraq Medical Journal, 6(1), 6–15. https://doi.org/10.22317/imj.v6i1.1148
Moroda, M., Takamoto, M., Iwakura, Y., Nakayama, J., & Aosai, F. (2017). Interleukin-17A-deficient mice are highly susceptible to Toxoplasma gondii infection due to excessively induced T. gondii HSP70 and interferon gamma production. Infection and Immunity, 85(12), 10-1128. https://doi.org/10.1128/iai.00399-17
Paerewijck, O., Maertens, B., Dreesen, L., Van Meulder, F., Peelaers, I., Ratman, D., ... & Geldhof, P. (2017). Interleukin-17 receptor A (IL-17RA) as a central regulator of the protective immune response against Giardia. Scientific Reports, 7(1), 8520. https://doi.org/10.1038/s41598-017-08590-x
Raouf-Rahmati, A., Ansar, A. R., Rezaee, S. A., Hosseini, S. M., Garweg, J. G., Ghezeldasht, S. A., ... & Moghaddas, E. (2021). Local and systemic gene expression levels of IL-10, IL-17 and TGF-β in active ocular toxoplasmosis in humans. Cytokine, 146, 155643. https://doi.org/10.1016/j.cyto.2021.155643
Saghaug, C. S., Sørnes, S., Peirasmaki, D., Svärd, S., Langeland, N., & Hanevik, K. (2016). Human memory CD4+ T cell immune responses against Giardia lamblia. Clinical and Vaccine Immunology, 23(1), 11-18. https://doi.org/10.1128/CVI.00419-15
Singer, S. M. (2016). Control of giardiasis by interleukin-17 in humans and mice—are the questions all answered?. Clinical and Vaccine Immunology, 23(1), 2-5. https://doi.org/10.1128/CVI.00648-15
Singh, T. P., Carvalho, A. M., Sacramento, L. A., Grice, E. A., & Scott, P. (2021). Microbiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis. PLoS Pathogens, 17(10), e1009693.https://doi.org/10.1371/journal.ppat.1009693
Terrazas, C., Varikuti, S., Kimble, J., Moretti, E., Boyaka, P. N., & Satoskar, A. R. (2015). IL-17A promotes susceptibility during experimental visceral leishmaniasis caused by Leishmania donovani. The FASEB Journal, 30(3), 1135–1143. https://doi.org/10.1096/fj.15-277202
Wang, C. C., Zhang, W. X., He, Y., Liu, J. H., Ju, C. S., Wu, Q. L., ... & Deng, S. Q. (2025). Global Epidemiology of Vector-Borne Parasitic Diseases: Burden, Trends, Disparities, and Forecasts (1990–2036). Pathogens, 14(9), 844. https://doi.org/10.3390/pathogens14090844
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Ismail, M., Amshawee, A., AL-Daher, R., Hussain, M., & Al-Fahham, A. (2026). The Protective Role of IL-17 Against Parasitic Infections: A Meta-Analysis Study. International Journal of Advancement in Life Sciences Research, 9(1), 32-41. https://doi.org/https://doi.org/10.31632/ijalsr.2026.v09i01.002
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