Effects of Cytokines IFN-γ and TGF-β on the Functional Activity of Blood Mononuclear Cells against Giardia lamblia
Background: This study aimed to analyze cultures of mononuclear (MN) cells with Giardia lamblia to determine the levels of the cytokines IFN-γ and TGF-β and the functional activity of MN cells after incubation with cytokines.
Methods: This study was conducted in 2018 in Barra do Garças, Mato Grosso State, Brazil. Blood samples were collected from 60 healthy volunteer donors to obtain leukocytes. The levels of IFN-γ and TGF-β were quantified in trophozoite cell culture supernatants. Superoxide release, phagocytosis, microbicidal activity, apoptosis and intracellular calcium release were analyzed.
Results: The cytokines evaluated were detected in the culture supernatant of MN cells and G. lamblia. Regardless of the type of cytokine, MN cells increased superoxide release in the presence of G. lamblia. Phagocytosis, microbicidal activity and apoptosis were higher when MN phagocytes were treated with cytokines. The highest microbicidal activity and apoptosis rates were observed in MN cells cultured with TGF-β. IFN-γ increased the release of intracellular calcium by MN phagocytes.
Conclusion: Cytokines play a beneficial role in the host by activating MN cells against G. lamblia. In addition, phagocytosis causes G. lamblia death and that the modulation of the functional activity of blood MN phagocytes by cytokines is an alternative mechanism for eliminating G. lamblia.
2. Astiazaran GH, Quintero J, Veja R, et al. Identification of T-cell stimulating antigens from Giardia lamblia by using Giardia-specific T-cell hybridomas. Parasite Immunol. 2009; 31(3):132-9.
3. Castillo-Villanueva A, Rufino-Gonzálezb Y, Méndeza ST, et al. Disulfiram as a novel inactivator of Giardia lamblia triosephosphate isomerase with antigiardial potential. Int J Parasitol Drugs Drug Resist. 2017: 7(3): 425–432.
4. Bartelt LA, Platts-Mills JA. Giardia: a pathogen or commensal for children in high prevalence settings? Curr Opin Infect Dis. 2016; 29(5): 502–507.
5. Cotton JA, Beatty JK, Buret AG. Host parasite interactions and pathophysiology in Giardia infections. Int J Parasitol. 2011; 41(9):925-33.
6. Fan K, Ruan Q, Sensenbrenner L, et al . Transforming growth factor-b bifunctionally regulates murine macrophage proliferation. Blood. 1992; 79(7):1679-85.
7. Roxstrom-Lindquist K, Palm D, et al . Giardia immunity--an update. Trends Parasitol. 2006; 22(1):26-31.
8. Teoh DA, Kamieniecki D, Pang G, et al . Giardia lamblia rearranjes F-actin and a-actinin in human colonic and duodenal monolayers and reduces transepithelial electrical resistanc. J Parasitol. 2000; 86(4):800-6.
9. Panaro MA, Cianciulli A, Mitolo V, et al. Caspase-dependent apoptosis of the HCT-8 epithelial cell line induced by the parasite Giardia intestinalis. FEMS Immunol Med Microbiol. 2007; 51(2):302-9.
10. Troeger H, Epple HJ, Schneider T, et al. Effect of chronic Giardia lamblia infection on epithelial transport and barrier function in human duodenum. Gut. 2007; 56(3): 328–335.
11. Chin AC, Teoh DA, Scott KGE, et al. Strain-dependent induction of enterocyte apoptosis by Giardia lamblia disrupts epithelial barrier function in a caspase-3-dependent manner. Infect Immun. 2002; 70(7):3673-80.
12. Singer SM, Nash TE. T-Cell-dependent control of acute Giardia lamblia infections in mice. Infect Immun. 2000; 68(1):170-5.
13. Fink MY, Singer SM. The Intersection of Immune Responses, Microbiota, and Pathogenesis in Giardiasis. Trends Parasitol. 2017; 33(11):901-913.
14. Hawrelak J. Giardiasis: pathophysiology and management. Altern Med Rev. 2003; 8(2):129-42.
15. Aluvihare VR, Kallikourdis M, Betz AG. Regulatory T cells mediate maternal tolerance to the fetus. Nature Immunol. 2004; 5(3):266-71.
16. Moraes LCA, França EL, Pessoa RS, et al. The effect of IFN-γ and TGF-β in the functional activity of mononuclear cells in the presence of Entamoeba histolytica. Parasit Vectors. 2015; 8: 413.
17. Jimenez JC, Morelle W, Michalsky JC, et al . Excreted⁄secreted glycoproteins of G intestinalis play an essential role in the antibody response. Parasitol Res. 2007; 100(4):715-20.
18. Honorio-França AC, Carvalho MP, Isaac L, et al . Colostral mononuclear phagocytes are able to kill Enteropathogenic Escherichia coli opsonized with colostral IgA. Scand J Immunol. 1997; 46(1):59-66.
19. Keister DB. Axenic culture of Giardia lamblia in TYI-S-33 medium supplemented with bile. Trans R Soc Trop Med Hyg. 1983; 77(4):487-8.
20. Hill DR, Pearson RD. Ingestion of Giardia lamblia trophozoites by human mononuclear phagocytes. Infect Immun. 1987; 55(12):3155-61.
21. Fagundes DLG, França EL, Morceli G, et al. The Role of Cytokines in the Functional Activity of Phagocytes in Blood and Colostrum of Diabetic Mothers. Clin Develop Immunol. 2013; 2013:590190.
22. Pick E, Mizel D. Rapid microassays for the measurement of superoxide and hydrogen peroxide production by macrophages in culture using an automatic enzyme immunoassay reader. J Immunol Methods. 1981; 46(2):211-26.
23. França-Botelho AC, Honorio-França AC, França EL, et al. Phagocytosis of Giardia lamblia trophozoites by human colostral leukocytes. Acta Paediatr. 2006; 95(4):438-43.
24. França EL, Bittencourt RV, Fujimori M, et al . Human colostral phagocytes eliminate enterotoxigenic Escherichia coli opsonized by colostrum supernatant. J Microbiol Immunol Infect. 2011; 44(1):1-7.
25. Hernandes MRG, Albuquerque LC, Ribeiro EB, et al . In vitro immunomodulatory effects of microemulsions with levamisole delivery systems on blood phagocytes interacting with Giardia lamblia. Parasitol Int. 2017; 66(3):299-304.
26. Boreham PFL. Giardiasis and its control. Pharm J. 1991; 234: 271–274.
27. Baeza IW, Alcantara-Hernandez M, Mancilla-Herrera, et al. The Role of Lipopeptidophosphoglycan in the Immune Response to Entamoeba histolytica. J Biomed Biotechnol. 2010; 2010:254521.
28. Corthésy B. Roundtrip ticket for secretory IgA: role in mucosal homeostasis? J Immunol. 2007; 178(1):27-32.
29. Celada A, Maki RA. Transforming growth factor-βl enhances the M-CSF and GM-CSF-stimulated proliferation of macrophages. J Immunol. 1992: 148(4):1102-5.
30. França-Botelho AC, França JL, Oliveira FMS, et al. Melatonin reduces the severity of experimental amoebiasis. Parasit Vectors. 2011; 4:62.
31. Pereira QLC, Hara CCP, Silva RT, et al . Human colostrum action against Giardia lamblia infection influenced by hormones and advanced maternal age. Parasitol Res. 2018; 117(6):1783-1791.
32. Casares S, Richie TL. Immune evasion by Malaria parasites: a challenge for vaccine development. Currt Opin Immunol. 2009; 21(3):321-30.
33. Pacheco-Yepez J, Jarillo-Luna RA, Gutierrez-Meza M, et al. Peroxynitrite and peroxiredoxin in the pathogenesis of experimental amebic liver abscess. Biomed Res Int. 2014; 2014:324230.
34. Fagundes DLG, França EL,Gonzatti MB, et al . The modulatory role of cytokines IL-4 and IL-17 in the functional activity of phagocytes in diabetic pregnant women. APMIS. 2018; 126(1):56-64.
35. Ribeiro E B, Kelly P, Lanes D, et al. Microemulsions with Levamisole Delivery Systems as Novel Immunomodulating Agents with Potential for Amebiasis Therapies. Science of Advanced Materials. 2015; 7(1): 15–27.
36. Dickson-Gonzalez SM, De-Uribe ML, Rodriguez-Morales AJ. Polymorphonuclear neutrophil infiltration intensity as consequence of Entamoeba histolytica density in amebic colitis. Surg Infect (Larchmt). 2009; 10(2):91-7.
37. Chadee K, Heerovitch E. Entamoeba histolytica: diffuse liver inflammation in gerbils (Meriones unguiculatus) with experimentally induced amebic liver abscesso. J Protozool. 1989; 36(2):154-8.
38. Novelli EL, Rodríguez NL, França EL, et al . High Dietary Carbohydrate and Panceatic lesion. Braz J Med Biol Res. 1993; 26(1):31-6.
39. Espino J, Bejarano I, Redondo PC, et al. Melatonin Reduces Apoptosis Induced by Calcium Signaling in Human Leukocytes: Evidence for the Involvement of Mitochondria and Bax Activation. J Memb Biol. 2010; 233(1-3):105-18.
40. Jiménez JC, Fontaine J, Grzych JM, et al . Systemic and mucosal responses to oral administration of excretory and secretory antigens from Giardia intestinalis. Clin Diag Lab Immunol. 2004: 11(1): 152–160.
|Issue||Vol 16 No 2 (2021)|
|Phagocytosis Cytokines Mononuclear cells Giardia lamblia|
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