Ex vivo infection of human placental chorionic villi explants with Trypanosoma cruzi and Toxoplasma gondii induces different Toll-like receptor expression and cytokine/chemokine profiles
Christian Castillo
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
Search for more papers by this authorLorena Muñoz
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
Search for more papers by this authorIleana Carrillo
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
Search for more papers by this authorAna Liempi
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
Search for more papers by this authorChristian Gallardo
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
Search for more papers by this authorNorbel Galanti
Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
Search for more papers by this authorJuan Diego Maya
Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
Search for more papers by this authorCorresponding Author
Ulrike Kemmerling
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
Correspondence
Ulrike Kemmerling, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
Email: [email protected]
Search for more papers by this authorChristian Castillo
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
Search for more papers by this authorLorena Muñoz
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
Search for more papers by this authorIleana Carrillo
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
Search for more papers by this authorAna Liempi
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
Search for more papers by this authorChristian Gallardo
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
Search for more papers by this authorNorbel Galanti
Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
Search for more papers by this authorJuan Diego Maya
Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
Search for more papers by this authorCorresponding Author
Ulrike Kemmerling
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
Correspondence
Ulrike Kemmerling, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
Email: [email protected]
Search for more papers by this authorAbstract
Problem
Trypanosoma cruzi and Toxoplasma gondii present, respectively, low and high congenital transmission rates. The placenta as an immune regulatory organ expresses TLRs, leading to the secretion of cytokines. Both parasites are recognized by TLR-2, TLR-4, and TLR-9. Here, we studied if the parasites induce differences in TLR protein expression, cytokine profiles, and whether receptor inhibition is related to parasite infection.
Method of study
Placental tissue explants were infected ex vivo with each parasite, TLRs protein expression, cytokine profile and parasite infection were determined by Western blotting, ELISA and qPCR.
Results
Trypanosoma cruzi and Toxoplasma gondii infection is related to TLR-2 and TLR-4/TLR-9, respectively. Trypanosoma cruzi elicits an increase in TNF-α, IL-1β, IL-6, IL-8 and IL-10 cytokine secretion whereas T. gondii only increases the secretion of IL-8.
Conclusion
The susceptibility of the placenta to each parasite is mediated partially by the innate immune response.
References
- 1Schmunis G. Status of and cost of Chagas disease worldwide. Lancet Infect Dis. 2013; 13: 283-284.
- 2Perez-Molina JA, Perez AM, Norman FF, Monge-Maillo B, Lopez-Velez R. Old and new challenges in Chagas disease. Lancet Infect Dis 2015; 15: 1347-1356.
- 3Melo MB, Jensen KD, Saeij JP. Toxoplasma gondii effectors are master regulators of the inflammatory response. Trends Parasitol. 2011; 27: 487-495.
- 4Robert-Gangneux F, Murat JB, Fricker-Hidalgo H, Brenier-Pinchart MP, Gangneux JP, Pelloux H. The placenta: a main role in congenital toxoplasmosis? Trends Parasitol. 2011; 27: 530-536.
- 5Liempi A, Castillo C, Duaso J, et al. Trypanosoma cruzi induces trophoblast differentiation: a potential local antiparasitic mechanism of the human placenta? Placenta 2014; 35: 1035-1042.
- 6Rendell VR, Gilman RH, Valencia E, et al. Trypanosoma cruzi-Infected Pregnant Women without Vector Exposure Have Higher Parasitemia Levels: Implications for Congenital Transmission Risk. PLoS ONE 2015; 10: e0119527.
- 7Carlier Y, Truyens C, Deloron P, Peyron F. Congenital parasitic infections: a review. Acta Trop. 2012; 121: 55-70.
- 8Berniscke K, Kaufmann P, Baergen RN. Pathology of the Human Placenta, 5th edition, New York, NY: Springer Science-Business Media, Inc. 1065; 2006.
- 9Duaso J, Rojo G, Cabrera G, et al. Trypanosoma cruzi induces tissue disorganization and destruction of chorionic villi in an ex vivo infection model of human placenta. Placenta. 2010; 31: 705-711.
- 10Mor G, Cardenas I. The immune system in pregnancy: a unique complexity. Am J Reprod Immunol. 2010; 63: 425-433.
- 11Koga K, Aldo PB, Mor G. Toll-like receptors and pregnancy: trophoblast as modulators of the immune response. J Obstet Gynaecol Res. 2009; 35: 191-202.
- 12Andrade WA, Souza Mdo C, Ramos-Martinez E, et al. Combined action of nucleic acid-sensing Toll-like receptors and TLR11/TLR12 heterodimers imparts resistance to Toxoplasma gondii in mice. Cell Host Microbe 2013; 13: 42-53.
- 13Dupont CD, Christian DA, Hunter CA. Immune response and immunopathology during toxoplasmosis. Semin Immunopathol. 2012; 34: 793-813.
- 14Tarleton RL. Immune system recognition of Trypanosoma cruzi. Curr Opin Immunol. 2007; 19: 430-434.
- 15Oviedo-Boyso J, Bravo-Patino A, Baizabal-Aguirre VM. Collaborative Action of Toll-Like and Nod-Like Receptors as Modulators of the Inflammatory Response to Pathogenic Bacteria. Mediators Inflamm. 2014; 2014: 432785.
- 16Yarovinsky F. Toll-like receptors and their role in host resistance to Toxoplasma gondii. Immunol Lett. 2008; 119: 17-21.
- 17Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol. 2014; 5: 461.
- 18Villalta F, Kierszenbaum F. Growth of isolated amastigotes of Trypanosoma cruzi in cell-free medium. J Protozool. 1982; 29: 570-576.
- 19Nardelli SC, Che FY, Silmon de Monerri NC, et al. The histone code of Toxoplasma gondii comprises conserved and unique posttranslational modifications. mBio 2013; 4: e00922-00913.
- 20Cummings KL, Tarleton RL. Rapid quantitation of Trypanosoma cruzi in host tissue by real-time PCR. Mol Biochem Parasitol. 2003; 129: 53-59.
- 21Lin MH, Chen TC, Kuo TT, Tseng CC, Tseng CP. Real-time PCR for quantitative detection of Toxoplasma gondii. J Clin Microbiol. 2000; 38: 4121-4125.
- 22Castillo C, Lopez-Munoz R, Duaso J, et al. Role of matrix metalloproteinases 2 and 9 in ex vivo Trypanosoma cruzi infection of human placental chorionic villi. Placenta. 2012; 33: 991-997.
- 23Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001; 29: e45.
- 24Sen R, Nayak L, De RK. A review on host-pathogen interactions: classification and prediction. Eur J Clin Microbiol Infect Dis 2016; 35: 1581-1599.
- 25Dos-Santos AL, Carvalho-Kelly LF, Dick CF, Meyer-Fernandes JR. Innate immunomodulation to trypanosomatid parasite infections. Exp Parasitol. 2016; 167: 67-75.
- 26Ghosh TK, Mickelson DJ, Fink J, et al. Toll-like receptor (TLR) 2-9 agonists-induced cytokines and chemokines: I. Comparison with T cell receptor-induced responses. Cell Immunol. 2006; 243: 48-57.
- 27Ponce NE, Cano RC, Carrera-Silva EA, Lima AP, Gea S, Aoki MP. Toll-like receptor-2 and interleukin-6 mediate cardiomyocyte protection from apoptosis during Trypanosoma cruzi murine infection. Med Microbiol Immunol. 2012; 201: 145-155.
- 28Nagajyothi F, Desruisseaux MS, Machado FS, et al. Response of adipose tissue to early infection with Trypanosoma cruzi (Brazil strain). J Infect Dis. 2012; 205: 830-840.
- 29Gopal R, Birdsell D, Monroy FP. Regulation of toll-like receptors in intestinal epithelial cells by stress and Toxoplasma gondii infection. Parasite Immunol. 2008; 30: 563-576.
- 30Bereswill S, Kuhl AA, Alutis M, et al. The impact of Toll-like-receptor-9 on intestinal microbiota composition and extra-intestinal sequelae in experimental Toxoplasma gondii induced ileitis. Gut Pathog. 2014; 6: 19.
- 31Sher A, Tosh K, Jankovic D. Innate recognition of Toxoplasma gondii in humans involves a mechanism distinct from that utilized by rodents. Cell Mol Immunol 2017; 14: 36-42.
- 32Hosein S, Rodriguez-Cortes A, Blake DP, Allenspach K, Alberola J, Solano-Gallego L. Transcription of Toll-Like Receptors 2, 3, 4 and 9, FoxP3 and Th17 Cytokines in a Susceptible Experimental Model of Canine Leishmania infantum Infection. PLoS ONE. 2015; 10: e0140325.
- 33Babiker DT, Bakhiet SM, Mukhtar MM. Leishmania donovani influenced cytokines and Toll-like receptors expression among Sudanese visceral leishmaniasis patients. Parasite Immunol. 2015; 37: 417-425.
- 34Chau A, Markley JC, Juang J, Tsen LC. Cytokines in the perinatal period - Part I. Int J Obstet Anesth. 2016; 26: 39-47.
- 35Verma R, Balakrishnan L, Sharma K, et al. A network map of Interleukin-10 signaling pathway. J Cell Commun Signal. 2016; 10: 61-67.
- 36Liempi A, Castillo C, Carrillo I, et al. A local innate immune response against Trypanosoma cruzi in the human placenta: the epithelial turnover of the trophoblast. Microb Pathog 2016; 99: 123-129.
- 37Munoz L, Castillo C, Carrillo I, et al. The Ex Vivo Infection of Human Placental Chorionic Villi Explants with Trypanosoma Cruzi and Toxoplasma Gondii Is Mediated by Different Toll-Like Receptors. Placenta. 2016; 45: 86-86.
- 38Mayer JP, Biancardi M, Altcheh J, Freilij H, Weinke T, Liesenfeld O. Congenital infections with Trypanosoma cruzi or Toxoplasma gondii are associated with decreased serum concentrations of interferon-gamma and interleukin-18 but increased concentrations of interleukin-10. Ann Trop Med Parasitol. 2010; 104: 485-492.
- 39Sturge CR, Benson A, Raetz M, et al. TLR-independent neutrophil-derived IFN-gamma is important for host resistance to intracellular pathogens. Proc Natl Acad Sci USA. 2013; 110: 10711-10716.
- 40Sturge CR, Yarovinsky F. Complex immune cell interplay in the gamma interferon response during Toxoplasma gondii infection. Infect Immun. 2014; 82: 3090-3097.
- 41Barbosa BF, Lopes-Maria JB, Gomes AO, et al. IL10, TGF beta1, and IFN gamma modulate intracellular signaling pathways and cytokine production to control Toxoplasma gondii infection in BeWo trophoblast cells. Biol Reprod. 2015; 92: 82.
- 42Murphy SP, Tayade C, Ashkar AA, Hatta K, Zhang J, Croy BA. Interferon gamma in successful pregnancies. Biol Reprod. 2009; 80: 848-859.