Abstract
Sarcocystis fusiformis is a coccidian tissue parasite that causes infection in buffalo in countries such an Egypt, China, Iraq and Iran, resulting in significant economic losses to the agricultural industry annually. There is a lack of studies examining host-parasite interactions at the level of the immune response and the present study investigates the interaction between S. fusiformis whole cyst antigens (SFWCA) and dendritic cells (DCs), cells critical to the activation of adaptive immunity. In this study bone marrow derived DCs (BMDCs) were phenotyped following treatment with SFWCA by measuring cell viability, cytokine secretion, and cell surface marker expression. While SFWCA exhibited cytotoxic effects on BMDCs at higher concentrations, lower concentrations of SFWCA activated pro-inflammatory DCs that significantly secreted interleukin (IL)-12p40, tumor necrosis factor alpha, IL-6 and IL-10. These cells also displayed enhanced expression of TLR4, CD80, CD86 and MHC II on their surface, which is indicative of full DCs maturation. Moreover, SFWCA significantly attenuated the capacity of BMDCs to suppress Th2 associated cytokines, notably IL-5 and IL-13, while simultaneously exhibiting no effects on the secretion of interferon (IFN)-γ, IL-2, IL-17, and IL-10. In conclusion, this is the first study to provide fundamental insight into the activation of DCs by SFWCA, providing us with some awareness into the interaction of the Sarcosystis parasite with its host. The pro-inflammatory inducing ability of this antigen is in keeping with studies performed in other protozoan parasites and therefore understanding these interactions is important in the development of future therapeutic strategies.
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References
Badawy AII, Abouzaid NZ, Ahmed HA (2012) Sarcocystis hominis and other Sarcocystis species infecting cattle at Sharkia Province, Egypt. Egypt J Am Sci 8:271–275
Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245. https://doi.org/10.1038/32588
Bedi B, Mead JR (2012) Cryptosporidium parvum antigens induce mouse and human dendritic cells to generate Th1-enhancing cytokines. Parasite Immunol 34:473–485. https://doi.org/10.1111/j.1365-3024.2012.01382.x
Bettiol E, Carapau D, Galan-Rodriguez C, Ocaña-Morgner C, Rodriguez A (2010) Dual effect of Plasmodium-infected erythrocytes on dendritic cell maturation. Malar J 9:64. https://doi.org/10.1186/1475-2875-9-64
Coban C, Ishii KJ, Kawai T, Hemmi H, Sato S, Uematsu S, Yamamoto M, Takeuchi O, Itagaki S, Kumar N, Horii T, Akira S (2005) Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin. J Exp Med 201:19–25. https://doi.org/10.1084/jem.20041836
Dong H, Su R, Wang Y, Tong Z, Zhang L, Yang Y, Hu J (2018) Sarcocystis species in wild and domestic sheep (Ovis ammon and Ovis aries) from China. BMC Vet Res 14:377. https://doi.org/10.1186/s12917-018-1712-9
Dubey JP, Fayer R, Rosenthal BM, Calero-Bernal R, Uggla A (2014) Identity of Sarcocystis species of the water buffalo (Bubalus bubalis) and cattle (Bos taurus) and the suppression of Sarcocystis sinensis as a nomen nudum. Vet Parasitol 205:1–6. https://doi.org/10.1016/j.vetpar.2014.06.020
Dubey JP, Calero-Bernal R, Rosenthal BM, Speer CA, Fayer R (2015) Sarcocystosis of animals and humans. CRC Press, Boca Raton, pp 1–481
El Shanawany EE, Nassar SA, Ata EB (2019) Detection of humoral and cellular immune responses in buffaloes naturally infected with sarcocystosis with risk factor assessment. Acta Vet 69:275–289. https://doi.org/10.2478/acve-2019-0023
El-Dakhly KM, El-Nesr KA, El-Nahass E-S, Hirata A, Sakai H, Yanai T (2011) Prevalence and distribution patterns of Sarcocystis spp. in buffaloes in Beni-Suef, Egypt. Trop Anim Health Prod 43:1549–1554. https://doi.org/10.1007/s11250-011-9840-2
Gazzinelli RT, Eltoum I, Wynn TA, Sher A (1993) Acute cerebral toxoplasmosis is induced by in vivo neutralization of TNF-alpha and correlates with the down-regulated expression of inducible nitric oxide synthase and other markers of macrophage activation. J Immunol 151:3672–3681
Ghoneim NH, Reda WMW, Nader MS (2014) Occurrence of Zoonotic Sarcosporidiosis in slaughtered Cattle and Buffaloes in different abattoirs in Egypt. Glob Vet 13:809–813. https://doi.org/10.5829/idosi.gv.2014.13.05.86211
Hamza T, Barnett JB, Li B (2010) Interleukin 12 a key immunoregulatory cytokine in infection applications. Int J Mol 11:789–806. https://doi.org/10.3390/ijms11030789
Hayashi S, Chan CC, Gazzinelli R, Roberge FG (1996) Contribution of nitric oxide to the host parasite equilibrium in toxoplasmosis. J Immunol 156:1476–1481
Huong LT, Uggla A (1999) Sarcocystis dubeyi n. sp. (Protozoa: sarcocystidae) in the water buffalo (Bubalus bubalis). J Parasitol 85:102–104. https://doi.org/10.2307/3285709
Janeway CA, Medzhitov R (2002) Innate immune recognition. Annu Rev Immunol 20:197–216. https://doi.org/10.1146/annurev.immuno
Kapsenberg ML (2003) Dendritic-cell control of pathogen-driven T-cell polarization. Nat Rev Immunol 3:984. https://doi.org/10.1038/nri1246
Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ (1951) Estimation of protein with the folin phenol reagent. J Biol Chem 193:265–275
Manicassamy S, Pulendran B (2011) Dendritic cell control of tolerogenic responses. Immunol Rev 241:206–227. https://doi.org/10.1111/j.1600-065X.2011.01015.x
McDowell MA, Marovich M, Lira R, Braun M, Sacks D (2002) Leishmania priming of human dendritic cells for CD40 ligand-induced interleukin-12p70 secretion is strain and species dependent. Infect Immun 70:3994–4001. https://doi.org/10.1128/IAI.70.8.3994-4001.2002
McKee AS, Dzierszinski F, Boes M, Roos DS, Pearce EJ (2004) Functional inactivation of immature dendritic cells by the intracellular parasite Toxoplasma gondii. J Immunol 173:2632–2640. https://doi.org/10.4049/jimmunol.173.4.2632
Metwally AM, Ellah MRA, AL-Hosary AA, Omar MA (2014) Microscopical and serological studies on Sarcocystis infection with first report of S. cruzi in buffaloes (Bubalus bubalis) in Assiut, Egypt. JOPD 38:378–382. https://doi.org/10.1007/s12639-013-0257-x
Mirzaei M, Rezaei H (2016) A survey on Sarcocystis spp. infection in cattle of Tabriz city, Iran. J Parasit Dis 40:648–651. https://doi.org/10.1007/s12639-014-0551-2
Morsy T, Abdel MM, Salama MM, Hamdi KN (1994) Assessment of intact Sarcocystis cystozoites as an ELISA antigen. J Egypt Soc Parasitol 24:85–91
Morsy K, Abdel-Ghaffar F, Dajem SB, Abdel-Gaber R, El Gazar F (2018) First molecular characterization and morphological aspects of Sarcocystis fusiformis infecting water buffalo Bubalus bubalis in Egypt. Acta Parasitol 63:333–345. https://doi.org/10.1515/ap-2018-0038
Olias P, Meyer A, Klopfleisch R, Lierz M, Kaspers B, Gruber AD (2013) Modulation of the host Th1 immune response in pigeon protozoal encephalitis caused by Sarcocystis calchasi. Vet Res 44:10. https://doi.org/10.1186/1297-9716-44-10
Poulsen CS, Stensvold CR (2014) Current status of epidemiology and diagnosis of human sarcocystosis. JCM 52:3524–3530. https://doi.org/10.1128/jcm.00955-14
Reichmann G, Walker W, Villegas EN, Craig L, Cai G, Alexander J, Hunter CA (2000) The CD40/CD40 ligand interaction is required for resistance to toxoplasmic encephalitis. Infect Immun 68:1312–1318. https://doi.org/10.1128/iai.68.3.1312-1318.2000
Sallusto F, Schaerli P, Loetscher P, Schaniel C, Lenig D, Mackay CR, Qin S, Lanzavecchia A (1998) Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation. Eur J Immunol 28:2760–2769. https://doi.org/10.1002/(SICI)1521-4141(199809)28:09%3c2760:AID-IMMU2760%3e3.0.CO;2-N
Sanecka A, Frickel EM (2012) Use and abuse of dendritic cells by Toxoplasma gondii. Virulence 3:678–689. https://doi.org/10.4161/viru.22833
Sayed FG, Shaheen MSI, Arafa MI, Koraa HM (2008) Sarcocystis infection in cattle at Assiut abattoir: microscopical and serological studies. Ass Univ Bull Environ Res 11:47–58
Schulz O, Edwards AD, Schito M, Aliberti J, Manickasingham S, Sher A, Reis e Sousa S (2000) CD40 triggering of heterodimeric IL-12 p70 production by dendritic cells in vivo requires a microbial priming signal. Immunity 13:453–462. https://doi.org/10.1016/s1074-7613(00)00045-5
Sheen JH, Strainic MG, Liu J, Zhang W, Yi Z, Medof ME, Heeger PS (2017) TLR-induced murine dendritic cell (DC) activation requires DC-intrinsic complement. J Immunol 199(1):278–291. https://doi.org/10.4049/jimmunol.1700339
Spencer JA, Deinnocentes P, Moyana EM, Guarino AJ, Ellison SE, Bird RC, Blagburn BL (2005) Cytokine gene expression in response to SnSAG1 in horses with equine protozoal myeloencephalitis. Clin Diagn Lab Immunol 12:644–646. https://doi.org/10.1128/CDLI.12.5.644-646.2005
Tappe D, Slesak G, Pérez-Girón JV, Schäfer J, Langeheinecke A, Just-Nübling G, Muñoz-Fontela C, Püllmann K (2015) Human invasive muscular Sarcocystosis Induces Th2 cytokine polarization and biphasic cytokine changes, based on an investigation among travelers returning from Tioman Island, Malaysia. Clin Vaccine Immunol 22:674–677. https://doi.org/10.1128/CVI.00042-15
Teixeira L, Botelho AS, Mesquita SD, Correia A, Cerca F, Costa R, Sampaio P, Castro AG, Vilanova M (2010) Plasmacytoid and conventional dendritic cells are early producers of IL-12 in Neospora caninum-infected mice. Immunol Cell Biol 88:79–86. https://doi.org/10.1038/icb.2009.65
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The authors are grateful to the Erasmus Staff mobility for Teaching and training assignments To/From Partner Countries for supporting this work.
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Connick, K., Lalor, R., Murphy, A. et al. Sarcocystis fusiformis whole cyst antigen activates pro-inflammatory dendritic cells. J Parasit Dis 44, 186–193 (2020). https://doi.org/10.1007/s12639-019-01181-9
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DOI: https://doi.org/10.1007/s12639-019-01181-9