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Congenital transmission of Mexican strains of Trypanosoma cruzi TcIa: interaction between parasite and human placental explants

Published online by Cambridge University Press:  24 November 2021

Cecilia Gomes Barbosa
Affiliation:
Laboratory of Parasitology, Department of Immunology, Microbiology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil
César Gómez-Hernández*
Affiliation:
Laboratory of Immunology, Department of Immunology, Microbiology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil
Marcos Vinícius da Silva
Affiliation:
Laboratory of Parasitology, Department of Immunology, Microbiology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil
Karine Rezende-Oliveira
Affiliation:
Laboratory of Biomedical Sciences, Federal University of Uberlandia – Pontal Institute of Exact and Natural Sciences, Ituiutaba, MG, Brazil
Paula Tatiana Mutão Ferreira
Affiliation:
Laboratory of Immunology, Department of Immunology, Microbiology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil
Ana Carolina Morais de Oliveira
Affiliation:
Laboratory of Immunology, Department of Immunology, Microbiology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil
Chamberttan Souza Desidério
Affiliation:
Laboratory of Immunology, Department of Immunology, Microbiology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil
Fernanda Rodrigues Helmo
Affiliation:
Laboratory of Immunology, Department of Immunology, Microbiology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil
Tamires Marielem de Carvalho-Costa
Affiliation:
Laboratory of Immunology, Department of Immunology, Microbiology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil
Ingrid Ketlen Pereira Dos Santos
Affiliation:
Laboratory of Immunology, Department of Immunology, Microbiology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil
Lorena Kelly Alves Saraiva
Affiliation:
Laboratory of Immunology, Department of Immunology, Microbiology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil
Carlo José Freire de Oliveira
Affiliation:
Laboratory of Immunology, Department of Immunology, Microbiology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil
Juliana Reis Machado
Affiliation:
Department of General Pathology, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil
Eloisa Amália Vieira Ferro
Affiliation:
Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Science, Federal University of Uberlândia, Campus Santa Mônica, Uberlândia, MG, Brazil
Virmondes Rodrigues Jr.
Affiliation:
Laboratory of Immunology, Department of Immunology, Microbiology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil
Luís Eduardo Ramirez
Affiliation:
Laboratory of Parasitology, Department of Immunology, Microbiology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil
*
Author for correspondence: César Gómez-Hernández, E-mail: cesar_cgh@hotmail.com

Abstract

Congenital transmission of Chagas disease plays an important role in endemic countries because it is not a diagnosis that is encountered frequently in prenatal care. Due to limited information regarding congenital transmission of Trypanosoma cruzi in Mexico, the present study aimed to investigate protozoan infectivity and modulation of immune responses in human placental explants infected with T. cruzi Ia Mexican strains. The Inc-5 strain showed increased infectivity and modulated IL-1β, IL-10 and TLR-4, decreasing their expression after 24 h of infection. Both strains (Inc-5 and Ninoa) stimulated the production of TNF-α and decreased IL-6 levels 96 h after infection. An important detachment of the syncytiotrophoblast caused by infection with T. cruzi was observed after 24 h of infection. In this study, ex vivo infection of human placental villi was performed to better understand interactions involving parasitic T. cruzi and human placental tissue. It was concluded that the strains of TcIa present parasitism in placental tissue, modulation of the innate immune system of the placenta, and cause intense detachment of the syncytiotrophoblast, a fact that may be more associated with abortion and premature birth events than the congenital transmission itself, justifying the low rate of this transmission mechanism by this genotype.

Type
Research Article
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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Footnotes

*

These authors contributed equally.

These senior authors contributed equally to this article.

References

Abrahams, VM, Bole-Aldo, P, Kim, YM, Straszewski-Chavez, SL, Chaiworapongsa, T, Romero, R and Mor, G (2004) Divergent trophoblast responses to bacterial products mediated by TLRs. Journal of Immunology 173, 42864296.CrossRefGoogle ScholarPubMed
Ander, SE, Diamond, MS and Coyne, CB (2019) Immune responses at the maternal-fetal interface. Science Immunology 4, eaat6114.CrossRefGoogle ScholarPubMed
Barbosa, CG, Carvalho Costa, TM, Desiderio, CS, Ferreira, PTM, Silva, MO, Hernandez, CG, Santos, MM, Trevisan, RO, Bovi, WG, Rodrigues, V, Machado, JR, Ramirez, LE, de Oliveira, CJF and da Silva, MV (2019 a) Trypanosoma cruzi Mexican strains differentially modulate surface markers and cytokine production in bone marrow-derived dendritic cells from C57BL/6 and BALB/c mice. Mediators of Inflammation 2019, 7214798.CrossRefGoogle ScholarPubMed
Barbosa, CG, Gomez-Hernandez, C, Rezende-Oliveira, K, Da Silva, MV, Rodrigues, JPF, Tiburcio, MGS, Ferreira, TB, Rodrigues, V, Yoshida, N and Ramirez, LE (2019 b) Oral infection of mice and host cell invasion by Trypanosoma cruzi strains from Mexico. Parasitology Research 118, 14931500.CrossRefGoogle ScholarPubMed
Basu, J, Agamasu, E, Bendek, B, Salafia, CM, Mishra, A, Benfield, N, Prasad, P and Mikhail, M (2016) Placental tumor necrosis factor-alpha protein expression during normal human gestation. The Journal of Maternal-Fetal & Neonatal Medicine 29, 39343938.CrossRefGoogle ScholarPubMed
Brogin Moreli, J, Cirino Ruocco, AM, Vernini, JM, Rudge, MV and Calderon, IM (2012) Interleukin 10 and tumor necrosis factor-alpha in pregnancy: aspects of interest in clinical obstetrics. ISRN Obstetrics & Gynecology 2012, 230742.CrossRefGoogle ScholarPubMed
Buekens, P, Cafferata, ML, Alger, J, Althabe, F, Belizan, JM, Carlier, Y, Ciganda, A, Dumonteil, E, Gamboa-Leon, R, Howard, E, Matute, ML, Sosa-Estani, S, Truyens, C, Wesson, D and Zuniga, C (2013) Congenital transmission of Trypanosoma cruzi in Argentina, Honduras, and Mexico: study protocol. Reproductive Health 10, 55.CrossRefGoogle ScholarPubMed
Bustos, PL, Milduberger, N, Volta, BJ, Perrone, AE, Laucella, SA and Bua, J (2019) Trypanosoma cruzi infection at the maternal-fetal interface: implications of parasite load in the congenital transmission and challenges in the diagnosis of infected newborns. Frontiers in Microbiology 10, 1250. doi: 10.3389/fmicb.2019.01250CrossRefGoogle Scholar
Carlier, Y and Truyens, C (2015) Congenital Chagas disease as an ecological model of interactions between Trypanosoma cruzi parasites, pregnant women, placenta and fetuses. Acta Tropica 151, 103115.CrossRefGoogle ScholarPubMed
Carlier, Y, Sosa-Estani, S, Luquetti, AO and Buekens, P (2015) Congenital Chagas disease: an update. Memorias Do instituto Oswaldo Cruz 110, 363368.CrossRefGoogle ScholarPubMed
Carlier, Y, Altcheh, J, Angheben, A, Freilij, H, Luquetti, AO, Schijman, AG, Segovia, M, Wagner, N and Albajar Vinas, P (2019) Congenital Chagas disease: updated recommendations for prevention, diagnosis, treatment, and follow-up of newborns and siblings, girls, women of childbearing age, and pregnant women. PLoS Neglected Tropical Diseases 13, e0007694.CrossRefGoogle ScholarPubMed
Carpentier, PA, Dingman, AL and Palmer, TD (2011) Placental TNF-alpha signaling in illness-induced complications of pregnancy. American Journal of Pathology 178, 28022810.CrossRefGoogle ScholarPubMed
Castillo, C, Villarroel, A, Duaso, J, Galanti, N, Cabrera, G, Maya, JD and Kemmerling, U (2013) Phospholipase C gamma and ERK1/2 mitogen activated kinase pathways are differentially modulated by Trypanosoma cruzi during tissue invasion in human placenta. Experimental Parasitology 133, 1217.CrossRefGoogle ScholarPubMed
Castillo, C, Munoz, L, Carrillo, I, Liempi, A, Gallardo, C, Galanti, N, Maya, JD and Kemmerling, U (2017) 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. American Journal of Reproductive Immunology 78, 18. doi: 10.1111/aji.12660CrossRefGoogle ScholarPubMed
Cura, CI, Mejia-Jaramillo, AM, Duffy, T, Burgos, JM, Rodriguero, M, Cardinal, MV, Kjos, S, Gurgel-Goncalves, R, Blanchet, D, De Pablos, LM, Tomasini, N, da Silva, A, Russomando, G, Cuba, CA, Aznar, C, Abate, T, Levin, MJ, Osuna, A, Gurtler, RE, Diosque, P, Solari, A, Triana-Chavez, O and Schijman, AG (2010) Trypanosoma cruzi I genotypes in different geographical regions and transmission cycles based on a microsatellite motif of the intergenic spacer of spliced-leader genes. International Journal for Parasitology 40, 15991607.CrossRefGoogle ScholarPubMed
del Puerto, R, Nishizawa, JE, Kikuchi, M, Iihoshi, N, Roca, Y, Avilas, C, Gianella, A, Lora, J, Velarde, FU, Renjel, LA, Miura, S, Higo, H, Komiya, N, Maemura, K and Hirayama, K (2010) Lineage analysis of circulating Trypanosoma cruzi parasites and their association with clinical forms of Chagas disease in Bolivia. PLoS Neglected Tropical Diseases 4, e687.CrossRefGoogle ScholarPubMed
Droguett, D, Carrillo, I, Castillo, C, Gomez, F, Negrete, M, Liempi, A, Munoz, L, Galanti, N, Maya, JD and Kemmerling, U (2017) Trypanosoma cruzi induces cellular proliferation in the trophoblastic cell line BeWo. Experimental Parasitology 173, 917.CrossRefGoogle ScholarPubMed
Duaso, J, Rojo, G, Cabrera, G, Galanti, N, Bosco, C, Maya, JD, Morello, A and Kemmerling, U (2010) Trypanosoma cruzi induces tissue disorganization and destruction of chorionic villi in an ex vivo infection model of human placenta. Placenta 31, 705711.CrossRefGoogle Scholar
Echeverria, LE and Morillo, CA (2019) American Trypanosomiasis (Chagas Disease). Infectious Disease Clinics of North America 33, 119134.CrossRefGoogle Scholar
Gómez-Hernández, C, Rezende-Oliveira, K, Nascentes, GAN, Batista, LR, Kappel, HB, Martinez-Ibarra, JA, Contreras, FT, Lages-Silva, E and Ramírez, LE (2011) Molecular characterization of Trypanosoma cruzi Mexican strains and their behavior in the mouse experimental model. Revista da Sociedade Brasileira de Medicina Tropical 44, 684690.CrossRefGoogle ScholarPubMed
Gómez-Hernández, C, Perez, SD, Rezende-Oliveira, K, Barbosa, CG, Lages-Silva, E, Ramirez, LE and Ramirez, JD (2019) Evaluation of the multispecies coalescent method to explore intra-Trypanosoma cruzi I relationships and genetic diversity. Parasitology 146, 10631074.CrossRefGoogle ScholarPubMed
Gonzalez, CI, Ortiz, S and Solari, A (2010) Colombian Trypanosoma cruzi major genotypes circulating in patients: minicircle homologies by cross-hybridization analysis. International Journal for Parasitology 40, 16851692.CrossRefGoogle ScholarPubMed
Guttmacher, AE, Maddox, YT and Spong, CY (2014) The human placenta project: placental structure, development, and function in real time. Placenta 35, 303304.CrossRefGoogle ScholarPubMed
Haider, S and Knofler, M (2009) Human tumour necrosis factor: physiological and pathological roles in placenta and endometrium. Placenta 30, 111123.CrossRefGoogle ScholarPubMed
Hayden, MS and Ghosh, S (2004) Signaling to NF-kappaB. Genes & Development 18, 21952224.CrossRefGoogle Scholar
Hunter, CA and Jones, SA (2015). IL-6 as a keystone cytokine in health and disease. Nature Immunology 16, 448457.CrossRefGoogle ScholarPubMed
Kemmerling, U, Castillo, C, Liempi, A, Medina, L, Carrillo, I, Droguett, D, Maya, JD and Galanti, N (2017) The immune response against Trypanosoma cruzi in the human placenta. Emerging Topics in Life Sciences 1, 573577.Google ScholarPubMed
Kemmerling, U, Osuna, A, Schijman, AG and Truyens, C (2019) Congenital transmission of Trypanosoma cruzi: a review about the interactions between the parasite, the placenta, the maternal and the fetal/neonatal immune responses. Frontiers in Microbiology 10, 1854. doi: 10.3389/fmicb.2019.01854CrossRefGoogle ScholarPubMed
Lawlor, KE, Feltham, R, Yabal, M, Conos, SA, Chen, KW, Ziehe, S, Graß, C, Zhan, Y, Nguyen, TA, Hall, C, Vince, AJ, Chatfield, SM, D'Silva, DB, Pang, KC, Schroder, K, Silke, J, Vaux, DL, Jost, PJ and Vince, JE (2017) XIAP loss triggers RIPK3- and caspase-8-driven IL-1β activation and cell death as a consequence of TLR-MyD88-induced cIAP1-TRAF2 degradation. Cell Reports 20, 668682.CrossRefGoogle ScholarPubMed
Lemmers, B, Salmena, L, Bidere, N, Su, H, Matysiak-Zablocki, E, Murakami, K, Ohashi, PS, Jurisicova, A, Lenardo, M, Hakem, R and Hakem, A (2007) Essential role for caspase-8 in Toll-like receptors and NFkappaB signaling. Journal of Biological Chemistry 282, 74167423.CrossRefGoogle ScholarPubMed
Liempi, A, Castillo, C, Duaso, J, Droguett, D, Sandoval, A, Barahona, K, Hernandez, A, Galanti, N, Maya, JD and Kemmerling, U (2014) Trypanosoma cruzi induces trophoblast differentiation: a potential local antiparasitic mechanism of the human placenta? Placenta 35, 10351042.CrossRefGoogle ScholarPubMed
Liempi, A, Castillo, C, Carrillo, I, Munoz, L, Droguett, D, Galanti, N, Maya, JD and Kemmerling, U (2016) A local innate immune response against Trypanosoma cruzi in the human placenta: the epithelial turnover of the trophoblast. Microbial Pathogenesis 99, 123129.CrossRefGoogle ScholarPubMed
Liempi, A, Castillo, C, Medina, L, Rojas-Pirela, M, Araneda, S, Maya, JD, Parraguez, VH and Kemmerling, U (2021) Ex vivo infection of canine and ovine placental explants with Trypanosoma cruzi and Toxoplasma gondii: differential activation of NF kappa B signaling pathways. Acta Tropica 214, 105766.CrossRefGoogle ScholarPubMed
Livak, KJ and Schmittgen, TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25, 402408.CrossRefGoogle Scholar
Luján, CD, Triquell, MF, Sembaj, A, Guerrero, CE and Fretes, ER (2004) Trypanosoma cruzi: productive infection is not allowed by chorionic villous explant from normal human placenta in vitro. Experimental Parasitology 108, 176181.CrossRefGoogle Scholar
Medina, L, Castillo, C, Liempi, A, Herbach, M, Cabrera, G, Valenzuela, L, Galanti, N, de Los Angeles Curto, M, Schijman, AG and Kemmerling, U (2018) Differential infectivity of two Trypanosoma cruzi strains in placental cells and tissue. Acta Tropica 186, 3540.CrossRefGoogle Scholar
Mejía-Jaramillo, AM, Fernández, GJ, Palacio, L and Triana-Chávez, O (2011) Gene expression study using real-time PCR identifies an NTR gene as a major marker of resistance to benzonidazole in Trypanosoma cruzi. Parasites & Vectors 4, 169.CrossRefGoogle ScholarPubMed
Messenger, LA and Bern, C (2018) Congenital Chagas disease: current diagnostics, limitations and future perspectives. Current Opinion in Infectious Diseases 31, 415421.CrossRefGoogle ScholarPubMed
Messenger, LA and Miles, MA (2015) Evidence and importance of genetic exchange among field populations of Trypanosoma cruzi. Acta Tropica 151, 150155.CrossRefGoogle ScholarPubMed
Mjihdi, A, Truyens, C, Detournay, O and Carlier, Y (2004) Systemic and placental productions of tumor necrosis factor contribute to induce fetal mortality in mice acutely infected with Trypanosoma cruzi. Experimental Parasitology 107, 5864.CrossRefGoogle ScholarPubMed
Monteon, V, Triana-Chavez, O, Mejia-Jaramillo, A, Pennignton, P, Ramos-Ligonio, A, Acosta, K and Lopez, R (2016) Circulation of Tc Ia discrete type unit Trypanosoma cruzi in Yucatan Mexico. Journal of Parasitic Diseases 40, 550554.CrossRefGoogle ScholarPubMed
Mor, G, Aldo, P and Alvero, AB (2017) The unique immunological and microbial aspects of pregnancy. Nature Reviews Immunology 17, 469482.CrossRefGoogle ScholarPubMed
Mukherjee, S, Karmakar, S and Babu, SP (2016) TLR2 and TLR4 mediated host immune responses in major infectious diseases: a review. The Brazilian Journal of Infectious Diseases 20, 193204.CrossRefGoogle ScholarPubMed
Olmos-Ortiz, A, Flores-Espinosa, P, Mancilla-Herrera, I, Vega-Sánchez, R, Díaz, L and Zaga-Clavellina, V (2019) Innate immune cells and Toll-like receptor-dependent responses at the maternal-fetal interface. International Journal of Molecular Sciences 20, 3654.CrossRefGoogle ScholarPubMed
Petersen, CA and Burleigh, BA (2003) Role for interleukin-1 beta in Trypanosoma cruzi-induced cardiomyocyte hypertrophy. Infection and Immunity 71, 44414447.CrossRefGoogle ScholarPubMed
Pino-Martínez, A M, Miranda, C G, Batalla, E I, González-Cappa, S M and Soto, Cda (2019) IL-10 participates in the expansion and functional activation of CD8 + T cells during acute infection with Trypanosoma cruzi. Journal of Leukocyte Biology 105, 163175.CrossRefGoogle ScholarPubMed
Ren, K and Torres, R (2009) Role of interleukin-1beta during pain and inflammation. Brain Research Reviews 60, 5764.CrossRefGoogle ScholarPubMed
Rendell, VR, Gilman, RH, Valencia, E, Galdos-Cardenas, G, Verastegui, M, Sanchez, L, Acosta, J, Sanchez, G, Ferrufino, L, LaFuente, C, Abastoflor Mdel, C, Colanzi, R and Bern, C (2015) Trypanosoma cruzi-infected pregnant women without vector exposure have higher parasitemia levels: implications for congenital transmission risk. PLoS ONE 10, e0119527.CrossRefGoogle ScholarPubMed
Rios, L, Campos, EE, Menon, R, Zago, MP and Garg, NJ (2020) Epidemiology and pathogenesis of maternal-fetal transmission of Trypanosoma cruzi and a case for vaccine development against congenital Chagas disease. Biochimica et Biophysica Acta Molecular Basis of Disease 1866, 165591.CrossRefGoogle Scholar
Rojo, G, Castillo, C, Duaso, J, Liempi, A, Droguett, D, Galanti, N, Maya, JD, Lopez-Munoz, R and Kemmerling, U (2014) Toxic and therapeutic effects of Nifurtimox and Benznidazol on Trypanosoma cruzi ex vivo infection of human placental chorionic villi explants. Acta Tropica 132, 112118.CrossRefGoogle ScholarPubMed
Santana, KH, Oliveira, LGR, Barros de Castro, D and Pereira, M (2020) Epidemiology of Chagas disease in pregnant women and congenital transmission of Trypanosoma cruzi in the Americas: systematic review and meta-analysis. Tropical Medicine & International Health 25, 752763.CrossRefGoogle ScholarPubMed
Soares, MJ, Varberg, KM and Iqbal, K (2018) Hemochorial placentation: development, function, and adaptations. Biology of Reproduction 99, 196211.CrossRefGoogle ScholarPubMed
Soriano-Arandes, A, Angheben, A, Serre-Delcor, N, Trevino-Maruri, B, Gomez, IPJ and Jackson, Y (2016) Control and management of congenital Chagas disease in Europe and other non-endemic countries: current policies and practices. Tropical Medicine & International Health 21, 590596.CrossRefGoogle ScholarPubMed
Tao, J, Yang, Z, Wang, JM, Wang, LC, Luo, CF, Tang, AL, Dong, YG and Ma, H (2007) Shear stress increases Cu/Zn SOD activity and mRNA expression in human endothelial progenitor cells. Journal of Human Hypertension 21, 353358.CrossRefGoogle ScholarPubMed
Torrico, MC, Solano, M, Guzman, JM, Parrado, R, Suarez, E, Alonzo-Vega, C, Truyens, C, Carlier, Y and Torrico, F (2005) [Estimation of the parasitemia in Trypanosoma cruzi human infection: high parasitemias are associated with severe and fatal congenital Chagas disease]. Revista da Sociedade Brasileira de Medicina Tropical 38(Suppl 2), 5861.Google Scholar
Volta, BJ, Perrone, AE, Rivero, R, Scollo, K, Bustos, PL and Bua, J (2018) Some limitations for early diagnosis of congenital Chagas infection by PCR. Pediatrics 141, S451S455.CrossRefGoogle ScholarPubMed
Yoshida, N, Teixeira, MM and Sbravate, CA (1986) Antigen characterization of vector-borne and cultured metacyclic trypomastigotes of Trypanosoma cruzi. Revista do Instituto de Medicina Tropical de Sao Paulo 28, 8086.CrossRefGoogle ScholarPubMed
Zingales, B (2018) Trypanosoma cruzi genetic diversity: something new for something known about Chagas disease manifestations, serodiagnosis and drug sensitivity. Acta Tropica 184, 3852.CrossRefGoogle ScholarPubMed
Zingales, B, Andrade, SG, Briones, MR, Campbell, DA, Chiari, E, Fernandes, O, Guhl, F, Lages-Silva, E, Macedo, AM, Machado, CR, Miles, MA, Romanha, AJ, Sturm, NR, Tibayrenc, M, Schijman, AG and Second Satellite, M (2009) A new consensus for Trypanosoma cruzi intraspecific nomenclature: second revision meeting recommends TcI to TcVI. Memorias Do instituto Oswaldo Cruz 104, 10511054.CrossRefGoogle ScholarPubMed